Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases

References

• Arrieta MC, Bistritz L, Meddings JB. Alterations in intestinal permeability. Gut 2006; 55:1512-20; PMID:16966705; http://dx.doi.org/10.1136/gut.2005.085373
   PubMed Web of Science ®Google Scholar
• Fasano A, Shea-Donohue T. Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol 2005; 2:416-22; PMID:16265432; http://dx.doi.org/10.1038/ncpgasthep0259
   PubMedGoogle Scholar
• Sapone A, de Magistris L, Pietzak M, Clemente MG, Tripathi A, Cucca F, Lampis R, Kryszak D, Cartenì M, Generoso M, et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes 2006; 55:1443-9; PMID:16644703; http://dx.doi.org/10.2337/db05-1593
   PubMed Web of Science ®Google Scholar
• Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 2002; 347:911-20; PMID:12239261; http://dx.doi.org/10.1056/NEJMra020100
   PubMed Web of Science ®Google Scholar
• Strachan DP. Hay fever, hygiene, and household size. BMJ 1989; 299:1259-60; PMID:2513902; http://dx.doi.org/10.1136/bmj.299.6710.1259
   PubMed Web of Science ®Google Scholar
• Noverr MC, Huffnagle GB. The ‘microflora hypothesis’ of allergic diseases. Clin Exp Allergy 2005; 35:1511-20; PMID:16393316; http://dx.doi.org/10.1111/j.1365-2222.2005.02379.x
   PubMed Web of Science ®Google Scholar
• Martin VJ, Leonard MM, Fiechtner L, Fasano A. Transitioning from descriptive to mechanistic understanding of the microbiome: the need for a prospective longitudinal approach to predicting disease. J Pediatr 2016; 30736-3; PMID: 27634626; http://dx.doi.org/10.1016/j.jpeds.2016.08.049
   Google Scholar
• Garcia-Lafuente A, Antolin M, Guarner F, Crespo E, Malagelada JR. Modulation of colonic barrier function by the composition of the commensal flora in the rat. Gut 2001; 48:503-7; PMID:11247894; http://dx.doi.org/10.1136/gut.48.4.503
   PubMed Web of Science ®Google Scholar
• Arrieta MC, Madsen K, Doyle J, Meddings J. Reducing small intestinal permeability attenuates colitis in the IL10 gene-deficient mouse. Gut 2009; 58:41-8; PMID:18829978; http://dx.doi.org/10.1136/gut.2008.150888
   PubMed Web of Science ®Google Scholar
• Visser JT, Lammers K, Hoogendijk A, Boer MW, Brugman S, Beijer-Liefers S, Zandvoort A, Harmsen H, Welling G, Stellaard F, et al. Restoration of impaired intestinal barrier function by the hydrolysed casein diet contributes to the prevention of type 1 diabetes in the diabetes-prone BioBreeding rat. Diabetologia 2010; 53:2621-8; PMID:20853098; http://dx.doi.org/10.1007/s00125-010-1903-9
   PubMed Web of Science ®Google Scholar
• Watts T, Berti I, Sapone A, Gerarduzzi T, Not T, Zielke R, Fasano A. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Natl Acad Sci U S A 2005; 102:2916-21; PMID:15710870; http://dx.doi.org/10.1073/pnas.0500178102
   PubMed Web of Science ®Google Scholar
• Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev 2011; 91:151-75; PMID:21248165; http://dx.doi.org/10.1152/physrev.00003.2008
   PubMed Web of Science ®Google Scholar
• Farquhar MG, Palade GE. Junctional complexes in various epithelia. J Cell Biol 1963; 17:375-412; PMID:13944428; http://dx.doi.org/10.1083/jcb.17.2.375
   PubMed Web of Science ®Google Scholar
• Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 2009; 9:799-809; PMID:19855405; http://dx.doi.org/10.1038/nri2653
   PubMed Web of Science ®Google Scholar
• Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S. Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 1993; 123:1777-88; PMID:8276896; http://dx.doi.org/10.1083/jcb.123.6.1777
   PubMed Web of Science ®Google Scholar
• Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S. Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 1998; 141:1539-50; PMID:9647647; http://dx.doi.org/10.1083/jcb.141.7.1539
   PubMed Web of Science ®Google Scholar
• Martin-Padura I, Lostaglio S, Schneemann M, Williams L, Romano M, Fruscella P, Panzeri C, Stoppacciaro A, Ruco L, Villa A, et al. Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. J Cell Biol 1998; 142:117-27; PMID:9660867; http://dx.doi.org/10.1083/jcb.142.1.117
   PubMed Web of Science ®Google Scholar
• Ikenouchi J, Furuse M, Furuse K, Sasaki H, Tsukita S, Tsukita S. Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells. J Cell Biol 2005; 171:939-45; PMID:16365161; http://dx.doi.org/10.1083/jcb.200510043
   PubMed Web of Science ®Google Scholar
• Higashi T, Tokuda S, Kitajiri S, Masuda S, Nakamura H, Oda Y, Furuse M. Analysis of the ‘angulin’ proteins LSR, ILDR1 and ILDR2–tricellulin recruitment, epithelial barrier function and implication in deafness pathogenesis. J Cell Sci 2013; 126:966-77; PMID:23239027; http://dx.doi.org/10.1242/jcs.116442
   PubMed Web of Science ®Google Scholar
• Noth R, Stuber E, Hasler R, Nikolaus S, Kuhbacher T, Hampe J, Bewig B, Schreiber S, Arlt A. Anti-TNF-α antibodies improve intestinal barrier function in Crohn's disease. J Crohns Colitis 2012; 6:464-9; PMID:22398062; http://dx.doi.org/10.1016/j.crohns.2011.10.004
   PubMed Web of Science ®Google Scholar
• Brown GR, Lindberg G, Meddings J, Silva M, Beutler B, Thiele D. Tumor necrosis factor inhibitor ameliorates murine intestinal graft-vs.-host disease. Gastroenterology 1999; 116:593-601; PMID:10029618; http://dx.doi.org/10.1016/S0016-5085(99)70181-2
   PubMed Web of Science ®Google Scholar
• Marafini I, Monteleone I, Di Fusco D, Cupi ML, Paoluzi OA, Colantoni A, Ortenzi A, Izzo R, Vita S, De Luca E, et al. TNF-α Producing Innate Lymphoid Cells (ILCs) Are Increased in Active Celiac Disease and Contribute to Promote Intestinal Atrophy in Mice. PLoS One 2015; 10:e0126291; PMID:25950701; http://dx.doi.org/10.1371/journal.pone.0126291
   PubMed Web of Science ®Google Scholar
• Shen L, Black ED, Witkowski ED, Lencer WI, Guerriero V, Schneeberger EE, Turner JR. Myosin light chain phosphorylation regulates barrier function by remodeling tight junction structure. J Cell Sci 2006; 119:2095-106; PMID:16638813; http://dx.doi.org/10.1242/jcs.02915
   PubMed Web of Science ®Google Scholar
• Su L, Shen L, Clayburgh DR, Nalle SC, Sullivan EA, Meddings JB, Abraham C, Turner JR. Targeted epithelial tight junction dysfunction causes immune activation and contributes to development of experimental colitis. Gastroenterology 2009; 136:551-63; PMID:19027740; http://dx.doi.org/10.1053/j.gastro.2008.10.081
   PubMed Web of Science ®Google Scholar
• Bruewer M, Utech M, Ivanov AI, Hopkins AM, Parkos CA, Nusrat A. Interferon-gamma induces internalization of epithelial tight junction proteins via a macropinocytosis-like process. FASEB J 2005; 19:923-33; PMID:15923402; http://dx.doi.org/10.1096/fj.04-3260com
   PubMed Web of Science ®Google Scholar
• Cario E, Rosenberg IM, Brandwein SL, Beck PL, Reinecker HC, Podolsky DK. Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing Toll-like receptors. J Immunol 2000; 164:966-72; PMID:10623846; http://dx.doi.org/10.4049/jimmunol.164.2.966
   PubMed Web of Science ®Google Scholar
• Cario E, Gerken G, Podolsky DK. Toll-like receptor 2 enhances ZO-1-associated intestinal epithelial barrier integrity via protein kinase C. Gastroenterology 2004; 127:224-38; PMID:15236188; http://dx.doi.org/10.1053/j.gastro.2004.04.015
   PubMed Web of Science ®Google Scholar
• Cario E, Gerken G, Podolsky DK. Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function. Gastroenterology 2007; 132:1359-74; PMID:17408640; http://dx.doi.org/10.1053/j.gastro.2007.02.056
   PubMed Web of Science ®Google Scholar
• Kong W, McConalogue K, Khitin LM, Hollenberg MD, Payan DG, Bohm SK, Bunnett NW. Luminal trypsin may regulate enterocytes through proteinase-activated receptor 2. Proc Natl Acad Sci U S A 1997; 94:8884-9; PMID:9238072; http://dx.doi.org/10.1073/pnas.94.16.8884
   PubMed Web of Science ®Google Scholar
• Darmoul D, Marie JC, Devaud H, Gratio V, Laburthe M. Initiation of human colon cancer cell proliferation by trypsin acting at protease-activated receptor-2. Br J Cancer 2001; 85:772-9; PMID:11531266; http://dx.doi.org/10.1054/bjoc.2001.1976
   PubMed Web of Science ®Google Scholar
• Coelho AM, Vergnolle N, Guiard B, Fioramonti J, Bueno L. Proteinases and proteinase-activated receptor 2: a possible role to promote visceral hyperalgesia in rats. Gastroenterology 2002; 122:1035-47; PMID:11910355; http://dx.doi.org/10.1053/gast.2002.32387
   PubMed Web of Science ®Google Scholar
• Chin AC, Vergnolle N, MacNaughton WK, Wallace JL, Hollenberg MD, Buret AG. Proteinase-activated receptor 1 activation induces epithelial apoptosis and increases intestinal permeability. Proc Natl Acad Sci U S A 2003; 100:11104-9; PMID:12960392; http://dx.doi.org/10.1073/pnas.1831452100
   PubMed Web of Science ®Google Scholar
• Mielants H, De Vos M, Goemaere S, Schelstraete K, Cuvelier C, Goethals K, Maertens M, Ackerman C, Veys EM. Intestinal mucosal permeability in inflammatory rheumatic diseases. II. Role of disease. J Rheumatol 1991; 18:394-400; PMID:1906939
   PubMed Web of Science ®Google Scholar
• Drago S, El Asmar R, Di Pierro M, Grazia Clemente M, Tripathi A, Sapone A, Thakar M, Iacono G, Carroccio A, D'Agate C, et al. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol 2006; 41:408-19; PMID:16635908; http://dx.doi.org/10.1080/00365520500235334
   PubMed Web of Science ®Google Scholar
• Fasano A, Not T, Wang W, Uzzau S, Berti I, Tommasini A, Goldblum SE. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet 2000; 355:1518-9; PMID:10801176; http://dx.doi.org/10.1016/S0140-6736(00)02169-3
   PubMed Web of Science ®Google Scholar
• Hollon J, Puppa EL, Greenwald B, Goldberg E, Guerrerio A, Fasano A. Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity. Nutrients 2015; 7:1565-76; PMID:25734566; http://dx.doi.org/10.3390/nu7031565
   PubMed Web of Science ®Google Scholar
• Camilleri M, Gorman H. Intestinal permeability and irritable bowel syndrome. Neurogastroenterol Motil 2007; 19:545-52; PMID:17593135; http://dx.doi.org/10.1111/j.1365-2982.2007.00925.x
   PubMed Web of Science ®Google Scholar
• Yacyshyn B, Meddings J, Sadowski D, Bowen-Yacyshyn MB. Multiple sclerosis patients have peripheral blood CD45RO+ B cells and increased intestinal permeability. Dig Dis Sci 1996; 41:2493-8; PMID:9011463; http://dx.doi.org/10.1007/BF02100148
   PubMed Web of Science ®Google Scholar
• Mooradian AD, Morley JE, Levine AS, Prigge WF, Gebhard RL. Abnormal intestinal permeability to sugars in diabetes mellitus. Diabetologia 1986; 29:221-4; PMID:3519337; http://dx.doi.org/10.1007/BF00454879
   PubMed Web of Science ®Google Scholar
• Benard A, Desreumeaux P, Huglo D, Hoorelbeke A, Tonnel AB, Wallaert B. Increased intestinal permeability in bronchial asthma. J Allergy Clin Immunol 1996; 97:1173-8; PMID:8648009; http://dx.doi.org/10.1016/S0091-6749(96)70181-1
   PubMed Web of Science ®Google Scholar
• Hijazi Z, Molla AM, Al-Habashi H, Muawad WM, Molla AM, Sharma PN. Intestinal permeability is increased in bronchial asthma. Arch Dis Child 2004; 89:227-9; PMID:14977697; http://dx.doi.org/10.1136/adc.2003.027680
   PubMed Web of Science ®Google Scholar
• Bergmann KR, Liu SX, Tian R, Kushnir A, Turner JR, Li HL, Chou PM, Weber CR, De Plaen IG. Bifidobacteria stabilize claudins at tight junctions and prevent intestinal barrier dysfunction in mouse necrotizing enterocolitis. Am J Pathol 2013; 182:1595-606; PMID:23470164; http://dx.doi.org/10.1016/j.ajpath.2013.01.013
   PubMed Web of Science ®Google Scholar
• Clark JA, Doelle SM, Halpern MD, Saunders TA, Holubec H, Dvorak K, Boitano SA, Dvorak B. Intestinal barrier failure during experimental necrotizing enterocolitis: protective effect of EGF treatment. Am J Physiol Gastrointest Liver Physiol 2006; 291:G938-49; PMID:16798726; http://dx.doi.org/10.1152/ajpgi.00090.2006
   PubMed Web of Science ®Google Scholar
• Hogberg N, Stenback A, Carlsson PO, Wanders A, Lilja HE. Genes regulating tight junctions and cell adhesion are altered in early experimental necrotizing enterocolitis. J Pediatr Surg 2013; 48:2308-12; PMID:24210204; http://dx.doi.org/10.1016/j.jpedsurg.2013.06.027
   PubMed Web of Science ®Google Scholar
• D'Eufemia P, Celli M, Finocchiaro R, Pacifico L, Viozzi L, Zaccagnini M, Cardi E, Giardini O. Abnormal intestinal permeability in children with autism. Acta Paediatr 1996; 85:1076-9; PMID:8888921; http://dx.doi.org/10.1111/j.1651-2227.1996.tb14220.x
   PubMed Web of Science ®Google Scholar
• Hermiston ML, Gordon JI. In vivo analysis of cadherin function in the mouse intestinal epithelium: essential roles in adhesion, maintenance of differentiation, and regulation of programmed cell death. J Cell Biol 1995; 129:489-506; PMID:7721948; http://dx.doi.org/10.1083/jcb.129.2.489
   PubMed Web of Science ®Google Scholar
• Hermiston ML, Gordon JI. Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin. Science 1995; 270:1203-7; PMID:7502046; http://dx.doi.org/10.1126/science.270.5239.1203
   PubMed Web of Science ®Google Scholar
• Laukoetter MG, Nava P, Lee WY, Severson EA, Capaldo CT, Babbin BA, Williams IR, Koval M, Peatman E, Campbell JA, et al. JAM-A regulates permeability and inflammation in the intestine in vivo. J Exp Med 2007; 204:3067-76; PMID:18039951; http://dx.doi.org/10.1084/jem.20071416
   PubMed Web of Science ®Google Scholar
• Naydenov NG, Feygin A, Wang D, Kuemmerle JF, Harris G, Conti MA, Adelstein RS, Ivanov AI. Nonmuscle Myosin IIA Regulates Intestinal Epithelial Barrier in vivo and Plays a Protective Role During Experimental Colitis. Sci Rep 2016; 6:24161; PMID:27063635; http://dx.doi.org/10.1038/srep24161
   PubMed Web of Science ®Google Scholar
• Irvine EJ, Marshall JK. Increased intestinal permeability precedes the onset of Crohn's disease in a subject with familial risk. Gastroenterology 2000; 119:1740-4; PMID:11113095; http://dx.doi.org/10.1053/gast.2000.20231
   PubMed Web of Science ®Google Scholar
• Boirivant M, Amendola A, Butera A, Sanchez M, Xu L, Marinaro M, Kitani A, Di Giacinto C, Strober W, Fuss IJ. A transient breach in the epithelial barrier leads to regulatory T-cell generation and resistance to experimental colitis. Gastroenterology 2008; 135:1612-23 e5; PMID:18765239; http://dx.doi.org/10.1053/j.gastro.2008.07.028
   PubMed Web of Science ®Google Scholar
• Iliev ID, Mileti E, Matteoli G, Chieppa M, Rescigno M. Intestinal epithelial cells promote colitis-protective regulatory T-cell differentiation through dendritic cell conditioning. Mucosal Immunol 2009; 2:340-50; PMID:19387433; http://dx.doi.org/10.1038/mi.2009.13
   PubMed Web of Science ®Google Scholar
• Fasano A, Baudry B, Pumplin DW, Wasserman SS, Tall BD, Ketley JM, Kaper JB. Vibrio cholerae produces a second enterotoxin, which affects intestinal tight junctions. Proc Natl Acad Sci U S A 1991; 88:5242-6; PMID:2052603; http://dx.doi.org/10.1073/pnas.88.12.5242
   PubMed Web of Science ®Google Scholar
• Fasano A, Fiorentini C, Donelli G, Uzzau S, Kaper JB, Margaretten K, Ding X, Guandalini S, Comstock L, Goldblum SE. Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro. J Clin Invest 1995; 96:710-20; PMID:7635964; http://dx.doi.org/10.1172/JCI118114
   PubMed Web of Science ®Google Scholar
• Fasano A, Uzzau S, Fiore C, Margaretten K. The enterotoxic effect of zonula occludens toxin on rabbit small intestine involves the paracellular pathway. Gastroenterology 1997; 112:839-46; PMID:9041245; http://dx.doi.org/10.1053/gast.1997.v112.pm9041245
   PubMed Web of Science ®Google Scholar
• Wang W, Uzzau S, Goldblum SE, Fasano A. Human zonulin, a potential modulator of intestinal tight junctions. J Cell Sci 2000; 113 Pt 24:4435-40; PMID:11082037
   PubMed Web of Science ®Google Scholar
• Tripathi A, Lammers KM, Goldblum S, Shea-Donohue T, Netzel-Arnett S, Buzza MS, Antalis TM, Vogel SN, Zhao A, Yang S, et al. Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proc Natl Acad Sci U S A 2009; 106:16799-804; PMID:19805376; http://dx.doi.org/10.1073/pnas.0906773106
   PubMed Web of Science ®Google Scholar
• Wicher KB, Fries E. Haptoglobin, a hemoglobin-binding plasma protein, is present in bony fish and mammals but not in frog and chicken. Proc Natl Acad Sci U S A 2006; 103:4168-73; PMID:16537503; http://dx.doi.org/10.1073/pnas.0508723103
   PubMed Web of Science ®Google Scholar
• Asleh R, Marsh S, Shilkrut M, Binah O, Guetta J, Lejbkowicz F, Enav B, Shehadeh N, Kanter Y, Lache O, et al. Genetically determined heterogeneity in hemoglobin scavenging and susceptibility to diabetic cardiovascular disease. Circ Res 2003; 92:1193-200; PMID:12750308; http://dx.doi.org/10.1161/01.RES.0000076889.23082.F1
   PubMed Web of Science ®Google Scholar
• Maeda N, Yang F, Barnett DR, Bowman BH, Smithies O. Duplication within the haptoglobin Hp2 gene. Nature 1984; 309:131-5; PMID:6325933; http://dx.doi.org/10.1038/309131a0
   PubMed Web of Science ®Google Scholar
• Wicher KB, Fries E. Prohaptoglobin is proteolytically cleaved in the endoplasmic reticulum by the complement C1r-like protein. Proc Natl Acad Sci U S A 2004; 101:14390-5; PMID:15385675; http://dx.doi.org/10.1073/pnas.0405692101
   PubMed Web of Science ®Google Scholar
• Kurosky A, Barnett DR, Lee TH, Touchstone B, Hay RE, Arnott MS, Bowman BH, Fitch WM. Covalent structure of human haptoglobin: a serine protease homolog. Proc Natl Acad Sci U S A 1980; 77:3388-92; PMID:6997877; http://dx.doi.org/10.1073/pnas.77.6.3388
   PubMed Web of Science ®Google Scholar
• Polticelli F, Bocedi A, Minervini G, Ascenzi P. Human haptoglobin structure and function–a molecular modelling study. FEBS J 2008; 275:5648-56; PMID:18959750; http://dx.doi.org/10.1111/j.1742-4658.2008.06690.x
   PubMed Web of Science ®Google Scholar
• Carter K, Worwood M. Haptoglobin: a review of the major allele frequencies worldwide and their association with diseases. Int J Lab Hematol 2007; 29:92-110; PMID:17474882; http://dx.doi.org/10.1111/j.1751-553X.2007.00898.x
   PubMed Web of Science ®Google Scholar
• Delanghe JR, Langlois MR, Boelaert JR, Van Acker J, Van Wanzeele F, van der Groen G, Hemmer R, Verhofstede C, De Buyzere M, De Bacquer D, et al. Haptoglobin polymorphism, iron metabolism and mortality in HIV infection. AIDS 1998; 12:1027-32; PMID:9662199; http://dx.doi.org/10.1097/00002030-199809000-00010
   PubMed Web of Science ®Google Scholar
• Kasvosve I, Gomo ZA, Mvundura E, Moyo VM, Saungweme T, Khumalo H, Gordeuk VR, Boelaert JR, Delanghe JR, De Bacquer D, et al. Haptoglobin polymorphism and mortality in patients with tuberculosis. Int J Tuberc Lung Dis 2000; 4:771-5; PMID:10949330
   PubMed Web of Science ®Google Scholar
• Papp M, Foldi I, Nemes E, Udvardy M, Harsfalvi J, Altorjay I, Mate I, Dinya T, Varvolgyi C, Barta Z, et al. Haptoglobin polymorphism: a novel genetic risk factor for celiac disease development and its clinical manifestations. Clinical Chemistry 2008; 54:697-704; PMID:18258668; http://dx.doi.org/10.1373/clinchem.2007.098780
   PubMed Web of Science ®Google Scholar
• Papp M, Lakatos PL, Palatka K, Foldi I, Udvardy M, Harsfalvi J, Altorjay I, Mate I, Dinya T, Varvolgyi C, et al. Haptoglobin polymorphisms are associated with Crohn's disease, disease behavior, and extraintestinal manifestations in Hungarian patients. Dig Dis Sci 2007; 52:1279-84; PMID:17357835; http://dx.doi.org/10.1007/s10620-006-9615-1
   PubMed Web of Science ®Google Scholar
• Vanuytsel T, Vermeire S, Cleynen I. The role of Haptoglobin and its related protein, Zonulin, in inflammatory bowel disease. Tissue Barriers 2013; 1:e27321; PMID:24868498; http://dx.doi.org/10.4161/tisb.27321
   PubMedGoogle Scholar
• Gloria-Bottini F, Lucarelli P, Saccucci P, Cozzoli E, Cerminara C, Curatolo P, Bottini E. Genetic polymorphism and idiopathic generalized epilepsy. Evidence of interaction between haptoglobin and ACP1 systems. Neuropediatrics 2008; 39:357-8; PMID:19569003; http://dx.doi.org/10.1055/s-0029-1202834
   PubMed Web of Science ®Google Scholar
• Maes M, Delanghe J, Bocchio Chiavetto L, Bignotti S, Tura GB, Pioli R, Zanardini R, Altamura CA, et al. Haptoglobin polymorphism and schizophrenia: genetic variation on chromosome 16. Psychiatry Res 2001; 104:1-9; PMID:11600184; http://dx.doi.org/10.1016/S0165-1781(01)00298-0
   PubMed Web of Science ®Google Scholar
• Nakhoul FM, Zoabi R, Kanter Y, Zoabi M, Skorecki K, Hochberg I, Leibu R, Miller B, Levy AP. Haptoglobin phenotype and diabetic nephropathy. Diabetologia 2001; 44:602-4; PMID:11380078; http://dx.doi.org/10.1007/s001250051666
   PubMed Web of Science ®Google Scholar
• Nakhoul FM, Marsh S, Hochberg I, Leibu R, Miller BP, Levy AP. Haptoglobin genotype as a risk factor for diabetic retinopathy. JAMA 2000; 284:1244-5; PMID:10979109; http://dx.doi.org/10.1001/jama.284.10.1244-a
   PubMed Web of Science ®Google Scholar
• Calderoni DR, Andrade Tdos S, Grotto HZ. Haptoglobin phenotype appears to affect the pathogenesis of American trypanosomiasis. Ann Trop Med Parasitol 2006; 100:213-21; PMID:16630378; http://dx.doi.org/10.1179/136485906X86356
   PubMedGoogle Scholar
• Jorge SE, Abreu CF, Guariento ME, Sonati Mde F. Haptoglobin genotypes in Chagas' disease. Clin Biochem 2010; 43:314-6; PMID:19804773; http://dx.doi.org/10.1016/j.clinbiochem.2009.09.020
   PubMed Web of Science ®Google Scholar
• Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 1992; 70:401-10; PMID:1643658; http://dx.doi.org/10.1016/0092-8674(92)90164-8
   PubMed Web of Science ®Google Scholar
• Ridley AJ, Hall A. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 1992; 70:389-99; PMID:1643657; http://dx.doi.org/10.1016/0092-8674(92)90163-7
   PubMed Web of Science ®Google Scholar
• Fasano A. Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin. Ann N Y Acad Sci 2000; 915:214-22; PMID:11193578; http://dx.doi.org/10.1111/j.1749-6632.2000.tb05244.x
   PubMed Web of Science ®Google Scholar
• van der Merwe JQ, Hollenberg MD, MacNaughton WK. EGF receptor transactivation and MAP kinase mediate proteinase-activated receptor-2-induced chloride secretion in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 2008; 294:G441-51; PMID:18032480; http://dx.doi.org/10.1152/ajpgi.00303.2007
   PubMedGoogle Scholar
• Lu R, Wang W, Uzzau S, Vigorito R, Zielke HR, Fasano A. Affinity purification and partial characterization of the zonulin/zonula occludens toxin (Zot) receptor from human brain. J Neurochem 2000; 74:320-6; PMID:10617135; http://dx.doi.org/10.1046/j.1471-4159.2000.0740320.x
   PubMed Web of Science ®Google Scholar
• Uzzau S, Lu R, Wang W, Fiore C, Fasano A. Purification and preliminary characterization of the zonula occludens toxin receptor from human (CaCo2) and murine (IEC6) intestinal cell lines. FEMS Microbiol Lett 2001; 194:1-5; PMID:11150657; http://dx.doi.org/10.1111/j.1574-6968.2001.tb09437.x
   PubMed Web of Science ®Google Scholar
• Goldblum SE, Rai U, Tripathi A, Thakar M, De Leo L, Di Toro N, Not T, Ramachandran R, Puche AC, Hollenberg MD, et al. The active Zot domain (aa 288-293) increases ZO-1 and myosin 1C serine/threonine phosphorylation, alters interaction between ZO-1 and its binding partners, and induces tight junction disassembly through proteinase activated receptor 2 activation. FASEB J 2011; 25:144-58; PMID:20852064; http://dx.doi.org/10.1096/fj.10-158972
   PubMed Web of Science ®Google Scholar
• McNeil E, Capaldo CT, Macara IG. Zonula occludens-1 function in the assembly of tight junctions in Madin-Darby canine kidney epithelial cells. Mol Biol Cell 2006; 17:1922-32; PMID:16436508; http://dx.doi.org/10.1091/mbc.E05-07-0650
   PubMed Web of Science ®Google Scholar
• El Asmar R, Panigrahi P, Bamford P, Berti I, Not T, Coppa GV, Catassi C, Fasano A. Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure. Gastroenterology 2002; 123:1607-15; PMID:12404235; http://dx.doi.org/10.1053/gast.2002.36578
   PubMed Web of Science ®Google Scholar
• Clemente MG, De Virgiliis S, Kang JS, Macatagney R, Musu MP, Di Pierro MR, Drago S, Congia M, Fasano A. Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut 2003; 52:218-23; PMID:12524403; http://dx.doi.org/10.1136/gut.52.2.218
   PubMed Web of Science ®Google Scholar
• Thomas KE, Sapone A, Fasano A, Vogel SN. Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in Celiac disease. J Immunol 2006; 176:2512-21; PMID:16456012; http://dx.doi.org/10.4049/jimmunol.176.4.2512
   PubMed Web of Science ®Google Scholar
• Clemente MG, Musu MP, Troncone R, Volta U, Congia M, Ciacci C, Neri E, Not T, Maggiore G, Strisciuglio P, et al. Enterocyte actin autoantibody detection: a new diagnostic tool in celiac disease diagnosis: results of a multicenter study. Am J Gastroenterol 2004; 99:1551-6; PMID:15307876; http://dx.doi.org/10.1111/j.1572-0241.2004.30296.x
   PubMed Web of Science ®Google Scholar
• Lammers KM, Lu R, Brownley J, Lu B, Gerard C, Thomas K, Rallabhandi P, Shea-Donohue T, Tamiz A, Alkan S, et al. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology 2008; 135:194-204 e3; PMID:18485912; http://dx.doi.org/10.1053/j.gastro.2008.03.023
   PubMed Web of Science ®Google Scholar
• Lammers KM, Khandelwal S, Chaudhry F, Kryszak D, Puppa EL, Casolaro V, Fasano A. Identification of a novel immunomodulatory gliadin peptide that causes interleukin-8 release in a chemokine receptor CXCR3-dependent manner only in patients with coeliac disease. Immunology 2010; 132(3):432-40; PMID:21091908
   PubMed Web of Science ®Google Scholar
• Fasano A. Intestinal zonulin: open sesame! Gut 2001; 49:159-62; PMID:11454785; http://dx.doi.org/10.1136/gut.49.2.159
   PubMed Web of Science ®Google Scholar
• Fasano A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall. Am J Pathol 2008; 173:1243-52; PMID:18832585; http://dx.doi.org/10.2353/ajpath.2008.080192
   PubMed Web of Science ®Google Scholar
• Smecuol E, Sugai E, Niveloni S, Vazquez H, Pedreira S, Mazure R, Moreno ML, Label M, Mauriño E, Fasano A, et al. Permeability, zonulin production, and enteropathy in dermatitis herpetiformis. Clin Gastroenterol Hepatol 2005; 3:335-41; PMID:15822038; http://dx.doi.org/10.1016/S1542-3565(04)00778-5
   PubMed Web of Science ®Google Scholar
• Di Pierro M, Lu R, Uzzau S, Wang W, Margaretten K, Pazzani C, Maimone F, Fasano A. Zonula occludens toxin structure-function analysis. Identification of the fragment biologically active on tight junctions and of the zonulin receptor binding domain. J Biol Chem 2001; 276:19160-5; PMID:11278543; http://dx.doi.org/10.1074/jbc.M009674200
   PubMed Web of Science ®Google Scholar
• Gopalakrishnan S, Tripathi A, Tamiz AP, Alkan SS, Pandey NB. Larazotide acetate promotes tight junction assembly in epithelial cells. Peptides 2012; 35:95-101; PMID:22401910; http://dx.doi.org/10.1016/j.peptides.2012.02.016
   PubMed Web of Science ®Google Scholar
• Gopalakrishnan S, Durai M, Kitchens K, Tamiz AP, Somerville R, Ginski M, Paterson BM, Murray JA, Verdu EF, Alkan SS, et al. Larazotide acetate regulates epithelial tight junctions in vitro and in vivo. Peptides 2012; 35:86-94; PMID:22401908; http://dx.doi.org/10.1016/j.peptides.2012.02.015
   PubMed Web of Science ®Google Scholar
• Black KE, Murray JA, David CS. HLA-DQ determines the response to exogenous wheat proteins: a model of gluten sensitivity in transgenic knockout mice. J Immunol 2002; 169:5595-600; PMID:12421937; http://dx.doi.org/10.4049/jimmunol.169.10.5595
   PubMed Web of Science ®Google Scholar
• de Kauwe AL, Chen Z, Anderson RP, Keech CL, Price JD, Wijburg O, Jackson DC, Ladhams J, Allison J, McCluskey J. Resistance to celiac disease in humanized HLA-DR3-DQ2-transgenic mice expressing specific anti-gliadin CD4+ T cells. J Immunol 2009; 182:7440-50; PMID:19494267; http://dx.doi.org/10.4049/jimmunol.0900233
   PubMed Web of Science ®Google Scholar
• Marietta E, Black K, Camilleri M, Krause P, Rogers RS, 3rd, David C, Pittelkow MR, Murray JA. A new model for dermatitis herpetiformis that uses HLA-DQ8 transgenic NOD mice. J Clin Invest 2004; 114:1090-7; PMID:15489956; http://dx.doi.org/10.1172/JCI200421055
   PubMed Web of Science ®Google Scholar
• Verdu EF, Huang X, Natividad J, Lu J, Blennerhassett PA, David CS, McKay DM, Murray JA. Gliadin-dependent neuromuscular and epithelial secretory responses in gluten-sensitive HLA-DQ8 transgenic mice. Am J Physiol Gastrointest Liver Physiol 2008; 294:G217-25; PMID:18006603; http://dx.doi.org/10.1152/ajpgi.00225.2007
   PubMed Web of Science ®Google Scholar
• Paterson BM, Lammers KM, Arrieta MC, Fasano A, Meddings JB. The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study. Aliment Pharmacol Ther 2007; 26:757-66; PMID:17697209; http://dx.doi.org/10.1111/j.1365-2036.2007.03413.x
   PubMed Web of Science ®Google Scholar
• Kelly CP, Green PH, Murray JA, Dimarino A, Colatrella A, Leffler DA, Alexander T, Arsenescu R, Leon F, Jiang JG, et al. Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study. Aliment Pharmacol Ther 2013; 37:252-62; PMID:23163616; http://dx.doi.org/10.1111/apt.12147
   PubMed Web of Science ®Google Scholar
• Leffler DA, Kelly CP, Abdallah HZ, Colatrella AM, Harris LA, Leon F, Arterburn LA, Paterson BM, Lan ZH, Murray JA. A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge. Am J Gastroenterol 2012; 107:1554-62; PMID:22825365; http://dx.doi.org/10.1038/ajg.2012.211
   PubMed Web of Science ®Google Scholar
• Leffler DA, Kelly CP, Green PH, Fedorak RN, DiMarino A, Perrow W, Rasmussen H, Wang C, Bercik P, Bachir NM, et al. Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial. Gastroenterology 2015; 148:1311-9 e6; PMID:25683116; http://dx.doi.org/10.1053/j.gastro.2015.02.008
   PubMed Web of Science ®Google Scholar
• Krumbhaar EB. Spontaneous Diabetes in a Dog. J Exp Med 1916; 24:361-5; PMID:19868047; http://dx.doi.org/10.1084/jem.24.4.361
   PubMedGoogle Scholar
• Feldman M, Schiller LR. Disorders of gastrointestinal motility associated with diabetes mellitus. Ann Intern Med 1983; 98:378-84; PMID:6402969; http://dx.doi.org/10.7326/0003-4819-98-3-378
   PubMed Web of Science ®Google Scholar
• Carratu R, Secondulfo M, de Magistris L, Iafusco D, Urio A, Carbone MG, Pontoni G, Cartenì M, Prisco F. Altered intestinal permeability to mannitol in diabetes mellitus type I. J Pediatr Gastroenterol Nutr 1999; 28:264-9; PMID:10067726; http://dx.doi.org/10.1097/00005176-199903000-00010
   PubMed Web of Science ®Google Scholar
• De Magistris L, Secondulfo M, Iafusco D, Carbone AG, Urio A, Pontoni G, Carratu R. Altered mannitol absorption in diabetic children. Ital J Gastroenterol 1996; 28:367; PMID:8891852
   PubMedGoogle Scholar
• Meddings JB, Jarand J, Urbanski SJ, Hardin J, Gall DG. Increased gastrointestinal permeability is an early lesion in the spontaneously diabetic BB rat. Am J Physiol 1999; 276:G951-7; PMID:10198339
   PubMed Web of Science ®Google Scholar
• Buhner S, Buning C, Genschel J, Kling K, Herrmann D, Dignass A, Kuechler I, Krueger S, Schmidt HH, Lochs H. Genetic basis for increased intestinal permeability in families with Crohn's disease: role of CARD15 3020insC mutation? Gut 2006; 55:342-7; PMID:16000642; http://dx.doi.org/10.1136/gut.2005.065557
   PubMed Web of Science ®Google Scholar
• Buning C, Geissler N, Prager M, Sturm A, Baumgart DC, Buttner J, Bühner S, Haas V, Lochs H. Increased small intestinal permeability in ulcerative colitis: rather genetic than environmental and a risk factor for extensive disease? Inflamm Bowel Dis 2012; 18:1932-9; PMID:22344959; http://dx.doi.org/10.1002/ibd.22909
   PubMed Web of Science ®Google Scholar
• Peeters M, Geypens B, Claus D, Nevens H, Ghoos Y, Verbeke G, Baert F, Vermeire S, Vlietinck R, Rutgeerts P. Clustering of increased small intestinal permeability in families with Crohn's disease. Gastroenterology 1997; 113:802-7; PMID:9287971; http://dx.doi.org/10.1016/S0016-5085(97)70174-4
   PubMed Web of Science ®Google Scholar
• Teahon K, Smethurst P, Levi AJ, Menzies IS, Bjarnason I. Intestinal permeability in patients with Crohn's disease and their first degree relatives. Gut 1992; 33:320-3; PMID:1568650; http://dx.doi.org/10.1136/gut.33.3.320
   PubMed Web of Science ®Google Scholar
• Wyatt J, Vogelsang H, Hubl W, Waldhoer T, Lochs H. Intestinal permeability and the prediction of relapse in Crohn's disease. Lancet 1993; 341:1437-9; PMID:8099141; http://dx.doi.org/10.1016/0140-6736(93)90882-H
   PubMed Web of Science ®Google Scholar
• Nouri M, Bredberg A, Westrom B, Lavasani S. Intestinal barrier dysfunction develops at the onset of experimental autoimmune encephalomyelitis, and can be induced by adoptive transfer of auto-reactive T cells. PLoS One 2014; 9:e106335; PMID:25184418; http://dx.doi.org/10.1371/journal.pone.0106335
   PubMed Web of Science ®Google Scholar
• Olszanecka-Glinianowicz M, Chudek J, Kocelak P, Szromek A, Zahorska-Markiewicz B. Body fat changes and activity of tumor necrosis factor α system–a 5-year follow-up study. Metabolism 2011; 60:531-6; PMID:20580040; http://dx.doi.org/10.1016/j.metabol.2010.04.023
   PubMed Web of Science ®Google Scholar
• Olszanecka-Glinianowicz M, Zahorska-Markiewicz B, Janowska J, Zurakowski A. Serum concentrations of nitric oxide, tumor necrosis factor (TNF)-α and TNF soluble receptors in women with overweight and obesity. Metabolism 2004; 53:1268-73; PMID:15375781; http://dx.doi.org/10.1016/j.metabol.2004.07.001
   PubMed Web of Science ®Google Scholar
• Zahorska-Markiewicz B, Janowska J, Olszanecka-Glinianowicz M, Zurakowski A. Serum concentrations of TNF-α and soluble TNF-α receptors in obesity. Int J Obes Relat Metab Disord 2000; 24:1392-5; PMID:11126333; http://dx.doi.org/10.1038/sj.ijo.0801398
   PubMed Web of Science ®Google Scholar
• Ferraris RP, Vinnakota RR. Intestinal nutrient transport in genetically obese mice. Am J Clin Nutr 1995; 62:540-6; PMID:7661115
   PubMed Web of Science ®Google Scholar
• Moreno-Navarrete JM, Sabater M, Ortega F, Ricart W, Fernandez-Real JM. Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance. PLoS One 2012; 7:e37160; PMID:22629362; http://dx.doi.org/10.1371/journal.pone.0037160
   PubMed Web of Science ®Google Scholar
• Zak-Golab A, Kocelak P, Aptekorz M, Zientara M, Juszczyk L, Martirosian G, Chudek J, Olszanecka-Glinianowicz M. Gut microbiota, microinflammation, metabolic profile, and zonulin concentration in obese and normal weight subjects. Int J Endocrinol 2013; 2013:674106; PMID:23970898; http://dx.doi.org/10.1155/2013/674106
   PubMed Web of Science ®Google Scholar
• Zhang D, Zhang L, Zheng Y, Yue F, Russell RD, Zeng Y. Circulating zonulin levels in newly diagnosed Chinese type 2 diabetes patients. Diabetes Res Clin Pract 2014; 106:312-8; PMID:25238913; http://dx.doi.org/10.1016/j.diabres.2014.08.017
   PubMed Web of Science ®Google Scholar
• Jayashree B, Bibin YS, Prabhu D, Shanthirani CS, Gokulakrishnan K, Lakshmi BS, Mohan V, Balasubramanyam M. Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes. Mol Cell Biochem 2014; 388:203-10; PMID:24347174; http://dx.doi.org/10.1007/s11010-013-1911-4
   PubMed Web of Science ®Google Scholar
• Oliviero S, Cortese R. The human haptoglobin gene promoter: interleukin-6-responsive elements interact with a DNA-binding protein induced by interleukin-6. EMBO J 1989; 8:1145-51; PMID:2787245
   PubMed Web of Science ®Google Scholar
• Pacifico L, Bonci E, Marandola L, Romaggioli S, Bascetta S, Chiesa C. Increased circulating zonulin in children with biopsy-proven nonalcoholic fatty liver disease. World J Gastroenterol 2014; 20:17107-14; PMID:25493023; http://dx.doi.org/10.3748/wjg.v20.i45.17107
   PubMed Web of Science ®Google Scholar
• Diamanti-Kandarakis E, Kandarakis H, Legro RS. The role of genes and environment in the etiology of PCOS. Endocrine 2006; 30:19-26; PMID:17185788; http://dx.doi.org/10.1385/ENDO:30:1:19
   PubMed Web of Science ®Google Scholar
• Zhang D, Zhang L, Yue F, Zheng Y, Russell R. Serum zonulin is elevated in women with polycystic ovary syndrome and correlates with insulin resistance and severity of anovulation. Eur J Endocrinol 2015; 172:29-36; PMID:25336505; http://dx.doi.org/10.1530/EJE-14-0589
   PubMed Web of Science ®Google Scholar
• Tremellen K, Pearce K. Dysbiosis of Gut Microbiota (DOGMA)–a novel theory for the development of Polycystic Ovarian Syndrome. Med Hypotheses 2012; 79:104-12; PMID:22543078; http://dx.doi.org/10.1016/j.mehy.2012.04.016
   PubMed Web of Science ®Google Scholar
• Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med 2000; 342:1334-49; PMID:10793167; http://dx.doi.org/10.1056/NEJM200005043421806
   PubMed Web of Science ®Google Scholar
• Rittirsch D, Flierl MA, Nadeau BA, Day DE, Huber-Lang MS, Grailer JJ, Zetoune FS, Andjelkovic AV, Fasano A, Ward PA. Zonulin as prehaptoglobin2 regulates lung permeability and activates the complement system. Am J Physiol Lung Cell Mol Physiol 2013; 304:L863-72; PMID:23564505; http://dx.doi.org/10.1152/ajplung.00196.2012
   PubMed Web of Science ®Google Scholar
• Eurich DT, Johnstone JJ, Minhas-Sandhu JK, Marrie TJ, Majumdar SR. Pneumococcal vaccination and risk of acute coronary syndromes in patients with pneumonia: population-based cohort study. Heart 2012; 98:1072-7; PMID:22739637; http://dx.doi.org/10.1136/heartjnl-2012-301743
   PubMed Web of Science ®Google Scholar
• Neumann T, Lulsdorf KA, Krings P, Reinsch N, Erbel R. Coronary artery disease in HIV-infected subjects. Results of 101 coronary angiographies. Herz 2011; 36:18-23
   PubMed Web of Science ®Google Scholar
• Vcev A, Nakic D, Mrden A, Mirat J, Balen S, Ruzic A, Persić V, Soldo I, Matijević M, Barbić J, et al. Helicobacter pylori infection and coronary artery disease. Coll Antropol 2007; 31:757-60; PMID:18041385
   PubMedGoogle Scholar
• Li C, Gao M, Zhang W, Chen C, Zhou F, Hu Z, Zeng C. Zonulin Regulates Intestinal Permeability and Facilitates Enteric Bacteria Permeation in Coronary Artery Disease. Sci Rep 2016; 6:29142; PMID:27353603; http://dx.doi.org/10.1038/srep29142
   PubMed Web of Science ®Google Scholar
• Diaz-Coranguez M, Segovia J, Lopez-Ornelas A, Puerta-Guardo H, Ludert J, Chavez B, Meraz-Cruz N, González-Mariscal L. Transmigration of neural stem cells across the blood brain barrier induced by glioma cells. PLoS One 2013; 8:e60655; PMID:23637756; http://dx.doi.org/10.1371/journal.pone.0060655
   PubMedGoogle Scholar
• Skardelly M, Armbruster FP, Meixensberger J, Hilbig H. Expression of Zonulin, c-kit, and Glial Fibrillary Acidic Protein in Human Gliomas. Transl Oncol 2009; 2:117-20; PMID:19701495; http://dx.doi.org/10.1593/tlo.09115
   PubMed Web of Science ®Google Scholar
• Yoseph BP, Klingensmith NJ, Liang Z, Breed ER, Burd EM, Mittal R, Dominguez JA, Petrie B, Ford ML, Coopersmith CM. Mechanisms of Intestinal Barrier Dysfunction in Sepsis. Shock 2016; 46:52-9; PMID:27299587; http://dx.doi.org/10.1097/SHK.0000000000000565
   PubMed Web of Science ®Google Scholar
• Klaus DA, Motal MC, Burger-Klepp U, Marschalek C, Schmidt EM, Lebherz-Eichinger D, Krenn CG, Roth GA. Increased plasma zonulin in patients with sepsis. Biochem Med (Zagreb) 2013; 23:107-11; PMID:23457771; http://dx.doi.org/10.11613/BM.2013.013
   PubMed Web of Science ®Google Scholar
• Liu Z, Li C, Huang M, Tong C, Zhang X, Wang L, Peng H, Lan P, Zhang P, Huang N, et al. Positive regulatory effects of perioperative probiotic treatment on postoperative liver complications after colorectal liver metastases surgery: a double-center and double-blind randomized clinical trial. BMC Gastroenterol 2015; 15:34; PMID:25881090; http://dx.doi.org/10.1186/s12876-015-0260-z
   PubMed Web of Science ®Google Scholar
• Deeks SG, Tracy R, Douek DC. Systemic effects of inflammation on health during chronic HIV infection. Immunity 2013; 39:633-45; PMID:24138880; http://dx.doi.org/10.1016/j.immuni.2013.10.001
   PubMed Web of Science ®Google Scholar
• Sandler NG, Wand H, Roque A, Law M, Nason MC, Nixon DE, Pedersen C, Ruxrungtham K, Lewin SR, Emery S, et al. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis 2011; 203:780-90; PMID:21252259; http://dx.doi.org/10.1093/infdis/jiq118
   PubMed Web of Science ®Google Scholar
• Tenorio AR, Zheng Y, Bosch RJ, Krishnan S, Rodriguez B, Hunt PW, Plants J, Seth A, Wilson CC, Deeks SG, et al. Soluble markers of inflammation and coagulation but not T-cell activation predict non-AIDS-defining morbid events during suppressive antiretroviral treatment. J Infect Dis 2014; 210:1248-59; PMID:24795473; http://dx.doi.org/10.1093/infdis/jiu254
   PubMed Web of Science ®Google Scholar
• Hunt PW, Sinclair E, Rodriguez B, Shive C, Clagett B, Funderburg N, Robinson J, Huang Y, Epling L, Martin JN, et al. Gut epithelial barrier dysfunction and innate immune activation predict mortality in treated HIV infection. J Infect Dis 2014; 210:1228-38; PMID:24755434; http://dx.doi.org/10.1093/infdis/jiu238
   PubMed Web of Science ®Google Scholar
• Serrano-Villar S, Sainz T, Ma ZM, Utay NS, Chun TW, Mann S, Kashuba AD, Siewe B, Albanese A, Troia-Cancio P, et al. Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naive to Antiretroviral Therapy: A Pilot Randomized Trial. PLoS Pathog 2016; 12:e1005540; PMID:27015639; http://dx.doi.org/10.1371/journal.ppat.1005540
   PubMedGoogle Scholar
• Barbaro MR, Cremon C, Caio G, Bellacosa L, De Giorgio R, Volta U, et al. The role of zonulin in non-celiac gluten sensitivity and irritable bowel syndrome. United Euro Gastroenterol J 2015; 3:A87
   Google Scholar
• Bueno L. Protease activated receptor 2: a new target for IBS treatment. Eur Rev Med Pharmacol Sci 2008; 12 Suppl 1:95-102; PMID:18924448
   PubMed Web of Science ®Google Scholar
• Kim JA, Choi SC, Yun KJ, Kim DK, Han MK, Seo GS, Yeom JJ, Kim TH, Nah YH, Lee YM. Expression of protease-activated receptor 2 in ulcerative colitis. Inflamm Bowel Dis 2003; 9:224-9; PMID:12902845; http://dx.doi.org/10.1097/00054725-200307000-00002
   PubMed Web of Science ®Google Scholar
• Gecse K, Roka R, Ferrier L, Rosztoczy A, Wittman T, Fioramonti J, et al. Elevated Fecal Serine-Protease Activity: Protease-Activated Receptor 2 (PAR2) Mediated Alteration of Colonic Permeability in Diarrhea-Predominant Irritable Bowel Syndrome. Gastroenterology 2007; 132:A-402
   Web of Science ®Google Scholar
• Vazquez-Roque MI, Camilleri M, Smyrk T, Murray JA, O'Neill J, Carlson P, Lamsam J, Eckert D, Janzow D, Burton D, et al. Association of HLA-DQ gene with bowel transit, barrier function, and inflammation in irritable bowel syndrome with diarrhea. Am J Physiol Gastrointest Liver Physiol 2012; 303:G1262-9; PMID:23042942; http://dx.doi.org/10.1152/ajpgi.00294.2012
   PubMed Web of Science ®Google Scholar
• Volta U, Caio G, Tovoli F, De Giorgio R. Non-celiac gluten sensitivity: questions still to be answered despite increasing awareness. Cell Mol Immunol 2013; 10:383-92; PMID:23934026; http://dx.doi.org/10.1038/cmi.2013.28
   PubMed Web of Science ®Google Scholar
• Guerrant RL, Leite AM, Pinkerton R, Medeiros PH, Cavalcante PA, DeBoer M, Kosek M, Duggan C, Gewirtz A, Kagan JC, et al. Biomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired Growth in Children in Northeast Brazil. PLoS One 2016; 11:e0158772; PMID:27690129; http://dx.doi.org/10.1371/journal.pone.0158772
   PubMedGoogle Scholar
• Rentea RM, Liedel JL, Welak SR, Cassidy LD, Mayer AN, Pritchard KA, Jr., Oldham KT, Gourlay DM. Intestinal alkaline phosphatase administration in newborns is protective of gut barrier function in a neonatal necrotizing enterocolitis rat model. J Pediatr Surg 2012; 47:1135-42; PMID:22703783; http://dx.doi.org/10.1016/j.jpedsurg.2012.03.018
   PubMed Web of Science ®Google Scholar
• Shiou SR, Yu Y, Chen S, Ciancio MJ, Petrof EO, Sun J, Claud EC. Erythropoietin protects intestinal epithelial barrier function and lowers the incidence of experimental neonatal necrotizing enterocolitis. J Biol Chem 2011; 286:12123-32; PMID:21262973; http://dx.doi.org/10.1074/jbc.M110.154625
   PubMed Web of Science ®Google Scholar
• Ling X, Linglong P, Weixia D, Hong W. Protective Effects of Bifidobacterium on Intestinal Barrier Function in LPS-Induced Enterocyte Barrier Injury of Caco-2 Monolayers and in a Rat NEC Model. PLoS One 2016; 11:e0161635; PMID:27551722; http://dx.doi.org/10.1371/journal.pone.0161635
   PubMed Web of Science ®Google Scholar