Pathophysiology of IBD associated diarrhea

References

• Zhang M, Sun K, Wu Y, Yang Y, Tso P, Wu Z. Interactions between Intestinal Microbiota and Host Immune Response in Inflammatory Bowel Disease. Front Immunol. 2017;8:942. doi:10.3389/fimmu.2017.00942.
   Web of Science ®Google Scholar
• Shouval DS, Rufo PA. The Role of Environmental Factors in the Pathogenesis of Inflammatory Bowel Diseases: A Review. JAMA pediatrics. 2017;171(10):999–1005. doi:10.1001/jamapediatrics.2017.2571. PMID: 28846760.
   PubMed Web of Science ®Google Scholar
• Priyamvada S, Gomes R, Gill RK, Saksena S, Alrefai WA, Dudeja PK. Mechanisms Underlying Dysregulation of Electrolyte Absorption in Inflammatory Bowel Disease-Associated Diarrhea. Inflamm Bowel Dis. 2015;21(12):2926–35. doi:10.1097/MIB.0000000000000504. PMID: 26595422.
   PubMed Web of Science ®Google Scholar
• Inflammatory Bowel Disease Is More Common Than Earlier Studies Showed. Jama. 2016;316(24):2590. doi:10.1001/jama.2016.18375..
   Google Scholar
• Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142(1):46–54 e42; quiz e30. doi:10.1053/j.gastro.2011.10.001. PMID: 22001864.
   PubMed Web of Science ®Google Scholar
• Ananthakrishnan AN. Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol. 2015;12(4):205–17. doi:10.1038/nrgastro.2015.34.
   PubMed Web of Science ®Google Scholar
• Umanskiy K, Fichera A. Health related quality of life in inflammatory bowel disease: the impact of surgical therapy. World J Gastroenterol. 2010;16(40):5024–34. PMID: 20976838.
   PubMed Web of Science ®Google Scholar
• Wenzl HH. Diarrhea in chronic inflammatory bowel diseases. Gastroenterol Clin North Am. 2012;41(3):651–75. doi:10.1016/j.gtc.2012.06.006. PMID: 22917170.
   PubMed Web of Science ®Google Scholar
• Binder HJ. Mechanisms of diarrhea in inflammatory bowel diseases. Ann N Y Acad Sci. 2009;1165:285–93. doi:10.1111/j.1749-6632.2009.04039.x.
   Web of Science ®Google Scholar
• Ward JB, Keely SJ, Keely SJ. Oxygen in the regulation of intestinal epithelial transport. J Physiol. 2014;592(12):2473–89. doi:10.1113/jphysiol.2013.270249. PMID: 24710059.
   PubMed Web of Science ®Google Scholar
• Seidler U, Lenzen H, Cinar A, Tessema T, Bleich A, Riederer B. Molecular mechanisms of disturbed electrolyte transport in intestinal inflammation. Ann N Y Acad Sci. 2006;1072:262–75. doi:10.1196/annals.1326.024..
   PubMed Web of Science ®Google Scholar
• Field M. Intestinal ion transport and the pathophysiology of diarrhea. J Clin Invest. 2003;111(7):931–43. doi:10.1172/JCI18326. PMID: 12671039.
   PubMed Web of Science ®Google Scholar
• Barkas F, Liberopoulos E, Kei A, Elisaf M. Electrolyte and acid-base disorders in inflammatory bowel disease. Ann Gastroenterol. 2013;26(1):23–8. PMID: 24714322.
   PubMedGoogle Scholar
• Sandle GI. Pathogenesis of diarrhea in ulcerative colitis: new views on an old problem. J Clin Gastroenterol. 2005;39(4 Suppl 2):S49–52. PMID: 15758659.
   PubMed Web of Science ®Google Scholar
• Surawicz CM. Mechanisms of diarrhea. Current gastroenterology reports. 2010;12(4):236–41. PMID: 20532705.
   PubMedGoogle Scholar
• Magalhaes D, Cabral JM, Soares-da-Silva P, Magro F. Role of epithelial ion transports in inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol. 2016;310(7):G460–76. doi:10.1152/ajpgi.00369.2015. PMID: 26744474.
   PubMed Web of Science ®Google Scholar
• McCole DF, Barrett KE. Decoding epithelial signals: critical role for the epidermal growth factor receptor in controlling intestinal transport function. Acta Physiol. 2009;195(1):149–59. doi:10.1111/j.1748-1716.2008.01929.x. PMID: 18983445.
   PubMed Web of Science ®Google Scholar
• Tang Y, Forsyth CB, Keshavarzian A. New molecular insights into inflammatory bowel disease-induced diarrhea. Expert Rev Gastroenterology Hepatol. 2011;5(5):615–25. doi:10.1586/egh.11.64.
   PubMed Web of Science ®Google Scholar
• Ghishan FK, Kiela PR. Epithelial transport in inflammatory bowel diseases. Inflamm Bowel Dis. 2014;20(6):1099–109. doi:10.1097/MIB.0000000000000029. PMID: 24691115.
   PubMed Web of Science ®Google Scholar
• Suh JS, Hahn WH, Cho BS. Recent Advances of Oral Rehydration Therapy (ORT). Electrolyte Blood Press: E & BP. 2010;8(2):82–6. doi:10.5049/EBP.2010.8.2.82.
   PubMedGoogle Scholar
• Gill RK, Alrefai W, Ramaswamy A, Dudeja PK. Mechanisms and regulation of NaCl absorption in the human intestine. Recent Res Devel Physiol. 2003;1:643–77.
   Google Scholar
• Martinez-Augustin O, Romero-Calvo I, Suarez MD, Zarzuelo A, de Medina FS. Molecular bases of impaired water and ion movements in inflammatory bowel diseases. Inflamm Bowel Dis. 2009;15(1):114–27. doi:10.1002/ibd.20579. PMID: 18626965.
   PubMed Web of Science ®Google Scholar
• Farkas K, Yeruva S, Rakonczay Z, Jr., Ludolph L, Molnar T, Nagy F, Szepes Z, Schnur A, Wittmann T, Hubricht J, et al. New therapeutic targets in ulcerative colitis: the importance of ion transporters in the human colon. Inflamm Bowel Dis. 2011;17(4):884–98. PMID: 20722063.
   PubMed Web of Science ®Google Scholar
• Barmeyer C, Erko I, Fromm A, Bojarski C, Allers K, Moos V, Zeitz M, Fromm M, Schulzke JD. Ion transport and barrier function are disturbed in microscopic colitis. Ann N Y Acad Sci. 2012;1258:143–8. doi:10.1111/j.1749-6632.2012.06631.x.
   PubMed Web of Science ®Google Scholar
• Amasheh S, Barmeyer C, Koch CS, Tavalali S, Mankertz J, Epple HJ, Gehring MM, Florian P, Kroesen AJ, Zeitz M, et al. Cytokine-dependent transcriptional down-regulation of epithelial sodium channel in ulcerative colitis. Gastroenterology. 2004;126(7):1711–20. PMID: 15188166.
   PubMed Web of Science ®Google Scholar
• Donowitz M, Ming Tse C, Fuster D. SLC9/NHE gene family, a plasma membrane and organellar family of Na(+)/H(+) exchangers. Mol Aspects Med. 2013;34(2-3):236–51. doi:10.1016/j.mam.2012.05.001. PMID: 23506868.
   PubMed Web of Science ®Google Scholar
• Kiela PR, Xu H, Ghishan FK. Apical NA+/H+ exchangers in the mammalian gastrointestinal tract. J Physiol Pharmacol. 2006;57 Suppl 7:51–59.
   PubMedGoogle Scholar
• Kiela PR, Ghishan FK. Na+-H+Exchange in Mammalian Digestive Tract. Physiology of the Gastrointestinal Tract (Fourth Edition). 2006;2:1847–1879.
   Google Scholar
• Xu H, Zhang B, Li J, Wang C, Chen H, Ghishan FK. Impaired mucin synthesis and bicarbonate secretion in the colon of NHE8 knockout mice. Am J Physiol Gastrointest Liver Physiol. 2012;303(3):G335–43. doi:10.1152/ajpgi.00146.2012. PMID: 22575219.
   PubMed Web of Science ®Google Scholar
• Zachos NC, Tse M, Donowitz M. Molecular physiology of intestinal Na+/H+ exchange. Annu Rev Physiol. 2005;67:411–443. doi:10.1146/annurev.physiol.67.031103.153004.
   PubMed Web of Science ®Google Scholar
• Gurney MA, Laubitz D, Ghishan FK, Kiela PR. Pathophysiology of Intestinal Na(+)/H(+) exchange. Cell Mol Gastroenterol Hepatol. 2017;3(1):27–40. doi:10.1016/j.jcmgh.2016.09.010. PMID: 28090568.
   PubMed Web of Science ®Google Scholar
• Khan I, al-Awadi FM, Abul H. Colitis-induced changes in the expression of the Na+/H+ exchanger isoform NHE-1. J Pharmacol Exp Ther. 1998;285(2):869–75. PMID: 9580638.
   PubMed Web of Science ®Google Scholar
• Khan I, Siddique I, Al-Awadi FM, Mohan K. Role of Na+/H+ exchanger isoform-1 in human inflammatory bowel disease. Canadian journal of gastroenterology = Journal canadien de gastroenterologie. 2003;17(1):31–6. PMID: 12560852.
   PubMedGoogle Scholar
• Siddique I, Khan I. Mechanism of regulation of Na-H exchanger in inflammatory bowel disease: role of TLR-4 signaling mechanism. Dig Dis Sci. 2011;56(6):1656–62. doi:10.1007/s10620-010-1524-7. PMID: 21221801.
   PubMed Web of Science ®Google Scholar
• Sullivan S, Alex P, Dassopoulos T, Zachos NC, Iacobuzio-Donahue C, Donowitz M, Brant SR, Cuffari C, Harris ML, Datta LW, et al. Downregulation of sodium transporters and NHERF proteins in IBD patients and mouse colitis models: potential contributors to IBD-associated diarrhea. Inflamm Bowel Dis. 2009;15(2):261–74. doi:10.1002/ibd.20743. PMID: 18942765.
   PubMed Web of Science ®Google Scholar
• Rocha F, Musch MW, Lishanskiy L, Bookstein C, Sugi K, Xie Y, Chang EB. IFN-gamma downregulates expression of Na(+)/H(+) exchangers NHE2 and NHE3 in rat intestine and human Caco-2/bbe cells. Am J Physiol Cell Physiol. 2001;280(5):C1224–32. doi:10.1152/ajpcell.2001.280.5.C1224. PMID: 11287336.
   PubMed Web of Science ®Google Scholar
• Amin MR, Orenuga T, Tyagi S, Dudeja PK, Ramaswamy K, Malakooti J. Tumor necrosis factor-alpha represses the expression of NHE2 through NF-kappaB activation in intestinal epithelial cell model, C2BBe1. Inflamm Bowel Dis. 2011;17(3):720–31. doi:10.1002/ibd.21419. PMID: 20722069.
   PubMed Web of Science ®Google Scholar
• Soleiman AA, Thameem F, Khan I. Mechanism of down regulation of Na-H exchanger-2 in experimental colitis. PloS One. 2017;12(5):e0176767. doi:10.1371/journal.pone.0176767. PMID: 28493993.
   PubMed Web of Science ®Google Scholar
• Xu H, Chen H, Dong J, Lynch R, Ghishan FK. Gastrointestinal distribution and kinetic characterization of the sodium-hydrogen exchanger isoform 8 (NHE8). Cellular physiology and biochemistry: international journal of experimental cellular physiology, biochemistry, and pharmacology. 2008;21(1-3):109–16. doi:10.1159/000113752. PMID: 18209477.
   PubMed Web of Science ®Google Scholar
• Liu C, Xu H, Zhang B, Johansson ME, Li J, Hansson GC, Ghishan FK. NHE8 plays an important role in mucosal protection via its effect on bacterial adhesion. Am J Physiol Cell Physiol. 2013;305(1):C121–8. doi:10.1152/ajpcell.00101.2013. PMID: 23657568.
   PubMed Web of Science ®Google Scholar
• Xu H, Chen H, Dong J, Li J, Chen R, Uno JK, Ghishan FK. Tumor necrosis factor-{alpha} downregulates intestinal NHE8 expression by reducing basal promoter activity. Am J Physiol Cell Physiol. 2009;296(3):C489–97. doi:10.1152/ajpcell.00482.2008. PMID: 19109523.
   PubMed Web of Science ®Google Scholar
• Wang A, Li J, Zhao Y, Johansson ME, Xu H, Ghishan FK. Loss of NHE8 expression impairs intestinal mucosal integrity. Am J Physiol Gastrointest Liver Physiol. 2015;309(11):G855–64. doi:10.1152/ajpgi.00278.2015. PMID: 26505975.
   PubMed Web of Science ®Google Scholar
• Xu H, Li Q, Zhao Y, Li J, Ghishan FK. Intestinal NHE8 is highly expressed in goblet cells and its expression is subject to TNF-alpha regulation. Am J Physiol Gastrointest Liver Physiol. 2016;310(2):G64–9. doi:10.1152/ajpgi.00367.2015. PMID: 26564720.
   PubMed Web of Science ®Google Scholar
• Schultheis PJ, Clarke LL, Meneton P, Miller ML, Soleimani M, Gawenis LR, Riddle TM, Duffy JJ, Doetschman T, Wang T, et al. Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H+ exchanger. Nat Genet. 1998;19(3):282–5. doi:10.1038/969. PMID: 9662405.
   PubMed Web of Science ®Google Scholar
• Gawenis LR, Stien X, Shull GE, Schultheis PJ, Woo AL, Walker NM, Clarke LL. Intestinal NaCl transport in NHE2 and NHE3 knockout mice. Am J Physiol Gastrointest Liver Physiol. 2002;282(5):G776–84. doi:10.1152/ajpgi.00297.2001. PMID: 11960774.
   PubMed Web of Science ®Google Scholar
• Ledoussal C, Woo AL, Miller ML, Shull GE. Loss of the NHE2 Na(+)/H(+) exchanger has no apparent effect on diarrheal state of NHE3-deficient mice. Am J Physiol Gastrointest Liver Physiol. 2001;281(6):G1385–96. doi:10.1152/ajpgi.2001.281.6.G1385. PMID: 11705743.
   PubMed Web of Science ®Google Scholar
• Janecke AR, Heinz-Erian P, Yin J, Petersen BS, Franke A, Lechner S, Fuchs I, Melancon S, Uhlig HH, Travis S, et al. Reduced sodium/proton exchanger NHE3 activity causes congenital sodium diarrhea. Hum Mol Genet. 2015;24(23):6614–23. doi:10.1093/hmg/ddv367. PMID: 26358773.
   PubMed Web of Science ®Google Scholar
• Zhu XC, Sarker R, Horton JR, Chakraborty M, Chen TE, Tse CM, Cha B, Donowitz M. Nonsynonymous single nucleotide polymorphisms of NHE3 differentially decrease NHE3 transporter activity. Am J Physiol Cell Physiol. 2015;308(9):C758–66. doi:10.1152/ajpcell.00421.2014. PMID: 25715704.
   PubMed Web of Science ®Google Scholar
• Janecke AR, Heinz-Erian P, Muller T. Congenital Sodium Diarrhea: A Form of Intractable Diarrhea, With a Link to Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr. 2016;63(2):170–6. doi:10.1097/MPG.0000000000001139. PMID: 26835907.
   PubMed Web of Science ®Google Scholar
• Anderson CA, Boucher G, Lees CW, Franke A, D'Amato M, Taylor KD, Lee JC, Goyette P, Imielinski M, Latiano A, et al. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet. 2011;43(3):246–52. doi:10.1038/ng.764. PMID: 21297633.
   PubMed Web of Science ®Google Scholar
• Yeruva S, Farkas K, Hubricht J, Rode K, Riederer B, Bachmann O, Cinar A, Rakonczay Z, Molnar T, Nagy F, et al. Preserved Na(+)/H(+) exchanger isoform 3 expression and localization, but decreased NHE3 function indicate regulatory sodium transport defect in ulcerative colitis. Inflamm Bowel Dis. 2010;16(7):1149–61. doi:10.1002/ibd.21183. PMID: 20027604.
   PubMed Web of Science ®Google Scholar
• Lohi H, Makela S, Pulkkinen K, Hoglund P, Karjalainen-Lindsberg ML, Puolakkainen P, Kere J. Upregulation of CFTR expression but not SLC26A3 and SLC9A3 in ulcerative colitis. Am J Physiol Gastrointest Liver Physiol. 2002;283(3):G567–75. doi:10.1152/ajpgi.00356.2001. PMID: 12181169.
   PubMed Web of Science ®Google Scholar
• Yeruva S, Chodisetti G, Luo M, Chen M, Cinar A, Ludolph L, Lunnemann M, Goldstein J, Singh AK, Riederer B, et al. Evidence for a causal link between adaptor protein PDZK1 downregulation and Na(+)/H(+) exchanger NHE3 dysfunction in human and murine colitis. Pflugers Archiv: European journal of physiology. 2015;467(8):1795–807. doi:10.1007/s00424-014-1608-x. PMID: 25271043.
   PubMed Web of Science ®Google Scholar
• Siddique I, Hasan F, Khan I. Suppression of Na+/H+ exchanger isoform-3 in human inflammatory bowel disease: lack of reversal by 5'-aminosalicylate treatment. Scand J Gastroenterol. 2009;44(1):56–64. doi:10.1080/00365520802321253. PMID: 18785066.
   PubMed Web of Science ®Google Scholar
• Lenzen H, Lunnemann M, Bleich A, Manns MP, Seidler U, Jorns A. Downregulation of the NHE3-binding PDZ-adaptor protein PDZK1 expression during cytokine-induced inflammation in interleukin-10-deficient mice. PloS one. 2012;7(7):e40657. doi:10.1371/journal.pone.0040657. PMID: 22848392.
   PubMed Web of Science ®Google Scholar
• Amin MR, Malakooti J, Sandoval R, Dudeja PK, Ramaswamy K. IFN-gamma and TNF-alpha regulate human NHE3 gene expression by modulating the Sp family transcription factors in human intestinal epithelial cell line C2BBe1. Am J Physiol Cell Physiol. 2006;291(5):C887–96. doi:10.1152/ajpcell.00630.2005. PMID: 16760259.
   PubMed Web of Science ®Google Scholar
• Clayburgh DR, Musch MW, Leitges M, Fu YX, Turner JR. Coordinated epithelial NHE3 inhibition and barrier dysfunction are required for TNF-mediated diarrhea in vivo. J Clin Invest. 2006;116(10):2682–94. doi:10.1172/JCI29218. PMID: 17016558.
   PubMed Web of Science ®Google Scholar
• Gill RK, Saksena S, Syed IA, Tyagi S, Alrefai WA, Malakooti J, Ramaswamy K, Dudeja PK. Regulation of NHE3 by nitric oxide in Caco-2 cells. Am J Physiol Gastrointest Liver Physiol. 2002;283(3):G747–56. doi:10.1152/ajpgi.00294.2001. PMID: 12181191.
   PubMed Web of Science ®Google Scholar
• Chen T, Kocinsky HS, Cha B, Murtazina R, Yang J, Tse CM, Singh V, Cole R, Aronson PS, de Jonge H, et al. Cyclic GMP kinase II (cGKII) inhibits NHE3 by altering its trafficking and phosphorylating NHE3 at three required sites: identification of a multifunctional phosphorylation site. J Biol Chem. 2015;290(4):1952–65. doi:10.1074/jbc.M114.590174. PMID: 25480791.
   PubMed Web of Science ®Google Scholar
• Muller T, Rasool I, Heinz-Erian P, Mildenberger E, Hulstrunk C, Muller A, Michaud L, Koot BG, Ballauff A, Vodopiutz J, et al. Congenital secretory diarrhoea caused by activating germline mutations in GUCY2C. Gut. 2016;65(8):1306–13. doi:10.1136/gutjnl-2015-309441. PMID: 25994218.
   PubMed Web of Science ®Google Scholar
• Laubitz D, Larmonier CB, Bai A, Midura-Kiela MT, Lipko MA, Thurston RD, Kiela PR, Ghishan FK. Colonic gene expression profile in NHE3-deficient mice: evidence for spontaneous distal colitis. Am J Physiol Gastrointest Liver Physiol. 2008;295(1):G63–77. doi:10.1152/ajpgi.90207.2008. PMID: 18467500.
   PubMed Web of Science ®Google Scholar
• Kiela PR, Laubitz D, Larmonier CB, Midura-Kiela MT, Lipko MA, Janikashvili N, Bai A, Thurston R, Ghishan FK. Changes in mucosal homeostasis predispose NHE3 knockout mice to increased susceptibility to DSS-induced epithelial injury. Gastroenterology. 2009;137(3):965–75, 75 e1-10. doi:10.1053/j.gastro.2009.05.043. PMID: 19450596.
   PubMed Web of Science ®Google Scholar
• Larmonier CB, Laubitz D, Thurston RD, Bucknam AL, Hill FM, Midura-Kiela M, Ramalingam R, Kiela PR, Ghishan FK. NHE3 modulates the severity of colitis in IL-10-deficient mice. Am J Physiol Gastrointest Liver Physiol. 2011;300(6):G998–G1009. doi:10.1152/ajpgi.00073.2011. PMID: 21415416.
   PubMed Web of Science ®Google Scholar
• Laubitz D, Harrison CA, Midura-Kiela MT, Ramalingam R, Larmonier CB, Chase JH, Caporaso JG, Besselsen DG, Ghishan FK, Kiela PR. Reduced Epithelial Na+/H+ Exchange Drives Gut Microbial Dysbiosis and Promotes Inflammatory Response in T Cell-Mediated Murine Colitis. PloS one. 2016;11(4):e0152044. doi:10.1371/journal.pone.0152044. PMID: 27050757.
   PubMed Web of Science ®Google Scholar
• Larmonier CB, Laubitz D, Hill FM, Shehab KW, Lipinski L, Midura-Kiela MT, McFadden RM, Ramalingam R, Hassan KA, Golebiewski M, et al. Reduced colonic microbial diversity is associated with colitis in NHE3-deficient mice. Am J Physiol Gastrointest Liver Physiol. 2013;305(10):G667–77. doi:10.1152/ajpgi.00189.2013. PMID: 24029465.
   PubMed Web of Science ®Google Scholar
• Firsov D, Gautschi I, Merillat AM, Rossier BC, Schild L. The heterotetrameric architecture of the epithelial sodium channel (ENaC). EMBO J. 1998;17(2):344–52. doi:10.1093/emboj/17.2.344. PMID: 9430626.
   PubMed Web of Science ®Google Scholar
• Greig E, Sandle GI. Diarrhea in ulcerative colitis. The role of altered colonic sodium transport. Ann N Y Acad Sci. 2000;915:327–32. PMID: 11193595.
   PubMed Web of Science ®Google Scholar
• Sandle GI, Higgs N, Crowe P, Marsh MN, Venkatesan S, Peters TJ. Cellular basis for defective electrolyte transport in inflamed human colon. Gastroenterology. 1990;99(1):97–105. PMID: 2344946.
   PubMed Web of Science ®Google Scholar
• Greig ER, Boot-Handford RP, Mani V, Sandle GI. Decreased expression of apical Na+ channels and basolateral Na+, K+-ATPase in ulcerative colitis. J Pathol. 2004;204(1):84–92. PMID: 15307141.
   PubMed Web of Science ®Google Scholar
• Zeissig S, Bergann T, Fromm A, Bojarski C, Heller F, Guenther U, Zeitz M, Fromm M, Schulzke JD. Altered ENaC expression leads to impaired sodium absorption in the noninflamed intestine in Crohn's disease. Gastroenterology. 2008;134(5):1436–47. PMID: 18355814.
   PubMed Web of Science ®Google Scholar
• McCole DF, Rogler G, Varki N, Barrett KE. Epidermal growth factor partially restores colonic ion transport responses in mouse models of chronic colitis. Gastroenterology. 2005;129(2):591–608. PMID: 16083715.
   PubMed Web of Science ®Google Scholar
• Bergann T, Zeissig S, Fromm A, Richter JF, Fromm M, Schulzke JD. Glucocorticoids and tumor necrosis factor-alpha synergize to induce absorption by the epithelial sodium channel in the colon. Gastroenterology. 2009;136(3):933–42. PMID: 19185581.
   PubMed Web of Science ®Google Scholar
• Barmeyer C, Harren M, Schmitz H, Heinzel-Pleines U, Mankertz J, Seidler U, Horak I, Wiedenmann B, Fromm M, Schulzke JD. Mechanisms of diarrhea in the interleukin-2-deficient mouse model of colonic inflammation. Am J Physiol Gastrointest Liver Physiol. 2004;286(2):G244–52. PMID: 14715519.
   PubMed Web of Science ®Google Scholar
• Umbach AT, Luo D, Bhavsar SK, Hosseinzadeh Z, Lang F. Intestinal Na+ loss and volume depletion in JAK3-deficient mice. Kidney & blood pressure research. 2013;37(4-5):514–20.
   PubMed Web of Science ®Google Scholar
• Toivola DM, Krishnan S, Binder HJ, Singh SK, Omary MB. Keratins modulate colonocyte electrolyte transport via protein mistargeting. J Cell Biol. 2004;164(6):911–21. PMID: 15007064.
   PubMed Web of Science ®Google Scholar
• Rajasekaran SA, Barwe SP, Rajasekaran AK. Multiple functions of Na,K-ATPase in epithelial cells. Semin Nephrol. 2005;25(5):328–34. doi:10.1016/j.semnephrol.2005.03.008. PMID: 16139688.
   PubMed Web of Science ®Google Scholar
• Hamilton KL, Robert K. Crane-Na(+)-glucose cotransporter to cure? Front Physiol. 2013;4:53. doi:10.3389/fphys.2013.00053.
   PubMed Web of Science ®Google Scholar
• Ewe K. Intestinal transport in constipation and diarrhoea. Pharmacology. 1988;36 Suppl 173–84.
   Google Scholar
• Allgayer H, Kruis W, Paumgartner G, Wiebecke B, Brown L, Erdmann E. Inverse relationship between colonic (Na+ + K+)-ATPase activity and degree of mucosal inflammation in inflammatory bowel disease. Dig Dis Sci. 1988;33(4):417–22. PMID: 2832138.
   PubMed Web of Science ®Google Scholar
• Ejderhamn J, Finkel Y, Strandvik B. Na,K-ATPase activity in rectal mucosa of children with ulcerative colitis and Crohn's disease. Scand J Gastroenterol. 1989;24(9):1121–5. PMID: 2556782.
   PubMed Web of Science ®Google Scholar
• Rachmilewitz D, Karmeli F, Sharon P. Decreased colonic Na-K-ATPase activity in active ulcerative colitis. Isr J Med Sci. 1984;20(8):681–4. PMID: 6088428.
   PubMedGoogle Scholar
• Hirota CL, McKay DM. Loss of Ca-mediated ion transport during colitis correlates with reduced ion transport responses to a Ca-activated K channel opener. Br J Pharmacol. 2009;156(7):1085–97. doi:10.1111/j.1476-5381.2009.00122.x. PMID: 19298254.
   PubMed Web of Science ®Google Scholar
• Magro F, Fraga S, Ribeiro T, Soares-da-Silva P. Regional intestinal adaptations in Na+,K+-ATPase in experimental colitis and the contrasting effects of interferon-gamma. Acta physiologica Scandinavica. 2005;183(2):191–9. doi:10.1111/j.1365-201X.2004.01388.x. PMID: 15676060.
   PubMedGoogle Scholar
• Wild GE, Thomson AB. Na(+)-K(+)-ATPase alpha 1- and beta 1-mRNA and protein levels in rat small intestine in experimental ileitis. Am J Physiol. 1995;269(5 Pt 1):G666–75. doi:10.1152/ajpgi.1995.269.5.G666. PMID: 7491957.
   PubMedGoogle Scholar
• Musch MW, Clarke LL, Mamah D, Gawenis LR, Zhang Z, Ellsworth W, Shalowitz D, Mittal N, Efthimiou P, Alnadjim Z, et al. T cell activation causes diarrhea by increasing intestinal permeability and inhibiting epithelial Na+/K+-ATPase. J Clin Invest. 2002;110(11):1739–47. doi:10.1172/JCI15695. PMID: 12464679.
   PubMed Web of Science ®Google Scholar
• Bertelsen LS, Eckmann L, Barrett KE. Prolonged interferon-gamma exposure decreases ion transport, NKCC1, and Na+-K+-ATPase expression in human intestinal xenografts in vivo. Am J Physiol Gastrointest Liver Physiol. 2004;286(1):G157–65. doi:10.1152/ajpgi.00227.2003. PMID: 12958023.
   PubMed Web of Science ®Google Scholar
• Yoo D, Lo W, Goodman S, Ali W, Semrad C, Field M. Interferon-gamma downregulates ion transport in murine small intestine cultured in vitro. Am J Physiol Gastrointest Liver Physiol. 2000;279(6):G1323–32. doi:10.1152/ajpgi.2000.279.6.G1323. PMID: 11093956.
   PubMed Web of Science ®Google Scholar
• Magro F, Fraga S, Ribeiro T, Soares-da-Silva P. Intestinal Na+-K+-ATPase activity and molecular events downstream of interferon-gamma receptor stimulation. Br J Pharmacol. 2004;142(8):1281–92. doi:10.1038/sj.bjp.0705895. PMID: 15277314.
   PubMed Web of Science ®Google Scholar
• Sugi K, Musch MW, Field M, Chang EB. Inhibition of Na+,K+-ATPase by interferon gamma down-regulates intestinal epithelial transport and barrier function. Gastroenterology. 2001;120(6):1393–403. PMID: 11313309.
   PubMed Web of Science ®Google Scholar
• Markossian S, Kreydiyyeh SI. TNF-alpha down-regulates the Na+-K+ ATPase and the Na+-K+-2Cl-cotransporter in the rat colon via PGE2. Cytokine. 2005;30(6):319–27. doi:10.1016/j.cyto.2004.11.009. PMID: 15935952.
   PubMed Web of Science ®Google Scholar
• Kreydiyyeh SI, Al-Sadi R. Interleukin-1beta increases urine flow rate and inhibits protein expression of Na(+)/K(+)-ATPase in the rat jejunum and kidney. Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research. 2002;22(10):1041–8. doi:10.1089/107999002760624279..
   PubMed Web of Science ®Google Scholar
• Al-Sadi RM, Kreydiyyeh SI. Mediators of interleukin-1 beta action Na(+)-K(+)ATPase in Caco-2 cells. Eur Cytokine Netw. 2003;14(2):83–90. PMID: 12957788.
   PubMed Web of Science ®Google Scholar
• Bachmann O, Seidler U. News from the end of the gut–how the highly segmental pattern of colonic HCO(3)(-) transport relates to absorptive function and mucosal integrity. Biological & pharmaceutical bulletin. 2011;34(6):794–802.
   PubMed Web of Science ®Google Scholar
• Roediger WE, Lawson MJ, Kwok V, Grant AK, Pannall PR. Colonic bicarbonate output as a test of disease activity in ulcerative colitis. J Clin Pathol. 1984;37(6):704–7. PMID: 6327778.
   PubMed Web of Science ®Google Scholar
• Caprilli R, Frieri G, Latella G, Vernia P, Santoro ML. Faecal excretion of bicarbonate in ulcerative colitis. Digestion. 1986;35(3):136–42. PMID: 3781109.
   PubMed Web of Science ®Google Scholar
• Schilli R, Breuer RI, Klein F, Dunn K, Gnaedinger A, Bernstein J, Paige M, Kaufman M. Comparison of the composition of faecal fluid in Crohn's disease and ulcerative colitis. Gut. 1982;23(4):326–32. PMID: 7076010.
   PubMed Web of Science ®Google Scholar
• Hawker PC, McKay JS, Turnberg LA. Electrolyte transport across colonic mucosa from patients with inflammatory bowel disease. Gastroenterology. 1980;79(3):508–11. PMID: 7429111.
   PubMed Web of Science ®Google Scholar
• Sandle GI, Hayslett JP, Binder HJ. Effect of glucocorticoids on rectal transport in normal subjects and patients with ulcerative colitis. Gut. 1986;27(3):309–16. PMID: 3699552.
   PubMed Web of Science ®Google Scholar
• Edmonds CJ, Pilcher D. Electrical potential difference and sodium and potassium fluxes across rectal mucosa in ulcerative colitis. Gut. 1973;14(10):784–9. PMID: 4758659.
   PubMed Web of Science ®Google Scholar
• Kato A, Romero MF. Regulation of electroneutral NaCl absorption by the small intestine. Annu Rev Physiol. 2011;73:261–81. doi:10.1146/annurev-physiol-012110-142244.
   PubMed Web of Science ®Google Scholar
• Mount DB, Romero MF. The SLC26 gene family of multifunctional anion exchangers. Pflugers Archiv: European journal of physiology. 2004;447(5):710–21. PMID: 12759755.
   PubMed Web of Science ®Google Scholar
• Alper SL, Sharma AK. The SLC26 gene family of anion transporters and channels. Mol Aspects Med. 2013;34(2-3):494–515. PMID: 23506885.
   PubMed Web of Science ®Google Scholar
• Makela S, Kere J, Holmberg C, Hoglund P. SLC26A3 mutations in congenital chloride diarrhea. Human mutation. 2002;20(6):425–38. PMID: 12442266.
   PubMed Web of Science ®Google Scholar
• Wedenoja S, Pekansaari E, Hoglund P, Makela S, Holmberg C, Kere J. Update on SLC26A3 mutations in congenital chloride diarrhea. Human mutation. 2011;32(7):715–22. PMID: 21394828.
   PubMed Web of Science ®Google Scholar
• Schweinfest CW, Spyropoulos DD, Henderson KW, Kim JH, Chapman JM, Barone S, Worrell RT, Wang Z, Soleimani M. slc26a3 (dra)-deficient mice display chloride-losing diarrhea, enhanced colonic proliferation, and distinct up-regulation of ion transporters in the colon. J Biol Chem. 2006;281(49):37962–71. PMID: 17001077.
   PubMed Web of Science ®Google Scholar
• Jiang Z, Asplin JR, Evan AP, Rajendran VM, Velazquez H, Nottoli TP, Binder HJ, Aronson PS. Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6. Nat Genet. 2006;38(4):474–8. doi:10.1038/ng1762. PMID: 16532010.
   PubMed Web of Science ®Google Scholar
• D'Angelo A, Bluteau O, Garcia-Gonzalez MA, Gresh L, Doyen A, Garbay S, Robine S, Pontoglio M. Hepatocyte nuclear factor 1alpha and beta control terminal differentiation and cell fate commitment in the gut epithelium. Development. 2010;137(9):1573–82. doi:10.1242/dev.044420. PMID: 20388655.
   PubMed Web of Science ®Google Scholar
• Borenshtein D, Schlieper KA, Rickman BH, Chapman JM, Schweinfest CW, Fox JG, Schauer DB. Decreased expression of colonic Slc26a3 and carbonic anhydrase iv as a cause of fatal infectious diarrhea in mice. Infect Immun. 2009;77(9):3639–50. PMID: 19546193.
   PubMed Web of Science ®Google Scholar
• Yang H, Jiang W, Furth EE, Wen X, Katz JP, Sellon RK, Silberg DG, Antalis TM, Schweinfest CW, Wu GD. Intestinal inflammation reduces expression of DRA, a transporter responsible for congenital chloride diarrhea. Am J Physiol. 1998;275(6 Pt 1):G1445–53. PMID: 9843783.
   PubMedGoogle Scholar
• Haila S, Saarialho-Kere U, Karjalainen-Lindsberg ML, Lohi H, Airola K, Holmberg C, Hastbacka J, Kere J, Hoglund P. The congenital chloride diarrhea gene is expressed in seminal vesicle, sweat gland, inflammatory colon epithelium, and in some dysplastic colon cells. Histochem Cell Biol. 2000;113(4):279–86. PMID: 10857479.
   PubMed Web of Science ®Google Scholar
• Singh V, Kumar A, Raheja G, Anbazhagan AN, Priyamvada S, Saksena S, Jhandier MN, Gill RK, Alrefai WA, Borthakur A, et al. Lactobacillus acidophilus attenuates downregulation of DRA function and expression in inflammatory models. Am J Physiol Gastrointest Liver Physiol. 2014;307(6):G623–31. doi:10.1152/ajpgi.00104.2014. PMID: 25059823.
   PubMed Web of Science ®Google Scholar
• Jayawardena D, Anbazhagan AN, Guzman G, Dudeja PK, Onyuksel H. Vasoactive Intestinal Peptide Nanomedicine for the Management of Inflammatory Bowel Disease. Molecular pharmaceutics. 2017;14(11):3698–708. doi:10.1021/acs.molpharmaceut.7b00452. PMID: 28991483.
   PubMed Web of Science ®Google Scholar
• Anbazhagan AN, Thaqi M, Priyamvada S, Jayawardena D, Kumar A, Gujral T, Chatterjee I, Mugarza E, Saksena S, Onyuksel H, et al. GLP-1 nanomedicine alleviates gut inflammation. Nanomedicine: nanotechnology, biology, and medicine. 2017;13(2):659–65. doi:10.1016/j.nano.2016.08.004. PMID: 27553076.
   PubMed Web of Science ®Google Scholar
• Xu L, Xiao F, He J, Lan X, Ding Q, Li J, Seidler U, Zheng Y, Tian D. Lysophosphatidic acid increases SLC26A3 expression in inflamed intestine and reduces diarrheal severity in C57BL/6 mice with dextran-sodium-sulfate-induced colitis. Chin Med J. 2014;127(9):1737–43. PMID: 24791884.
   PubMed Web of Science ®Google Scholar
• Kumar A, Anbazhagan AN, Coffing H, Chatterjee I, Priyamvada S, Gujral T, Saksena S, Gill RK, Alrefai WA, Borthakur A, et al. Lactobacillus acidophilus counteracts inhibition of NHE3 and DRA expression and alleviates diarrheal phenotype in mice infected with Citrobacter rodentium. Am J Physiol Gastrointest Liver Physiol. 2016;311(5):G817–G26. doi:10.1152/ajpgi.00173.2016. PMID: 27634011.
   PubMed Web of Science ®Google Scholar
• Xiao F, Juric M, Li J, Riederer B, Yeruva S, Singh AK, Zheng L, Glage S, Kollias G, Dudeja P, et al. Loss of downregulated in adenoma (DRA) impairs mucosal HCO3(-) secretion in murine ileocolonic inflammation. Inflamm Bowel Dis. 2012;18(1):101–11. doi:10.1002/ibd.21744. PMID: 21557395.
   PubMed Web of Science ®Google Scholar
• Asano K, Matsushita T, Umeno J, Hosono N, Takahashi A, Kawaguchi T, Matsumoto T, Matsui T, Kakuta Y, Kinouchi Y, et al. A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population. Nat Genet. 2009;41(12):1325–9. doi:10.1038/ng.482. PMID: 19915573.
   PubMed Web of Science ®Google Scholar
• Xiao F, Yu Q, Li J, Johansson ME, Singh AK, Xia W, Riederer B, Engelhardt R, Montrose M, Soleimani M, et al. Slc26a3 deficiency is associated with loss of colonic HCO3 (-) secretion, absence of a firm mucus layer and barrier impairment in mice. Acta Physiol. 211(1):161–75. PMID: 24373192.
   PubMed Web of Science ®Google Scholar
• Johansson ME, Gustafsson JK, Holmen-Larsson J, Jabbar KS, Xia L, Xu H, Ghishan FK, Carvalho FA, Gewirtz AT, Sjovall H, et al. Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis. Gut. 2014;63(2):281–91. doi:10.1136/gutjnl-2012-303207. PMID: 23426893.
   PubMed Web of Science ®Google Scholar
• Serafini EP, Kirk AP, Chambers TJ. Rate and pattern of epithelial cell proliferation in ulcerative colitis. Gut. 1981;22(8):648–52. PMID: 7286781.
   PubMed Web of Science ®Google Scholar
• Saksena S, Singla A, Goyal S, Katyal S, Bansal N, Gill RK, Alrefai WA, Ramaswamy K, Dudeja PK. Mechanisms of transcriptional modulation of the human anion exchanger SLC26A3 gene expression by IFN-{gamma}. Am J Physiol Gastrointest Liver Physiol. 2010;298(2):G159–66. doi:10.1152/ajpgi.00374.2009. PMID: 19940027.
   PubMed Web of Science ®Google Scholar
• Kumar A, Chatterjee I, Gujral T, Alakkam A, Coffing H, Anbazhagan AN, Borthakur A, Saksena S, Gill RK, Alrefai WA, et al. Activation of Nuclear Factor-kappaB by Tumor Necrosis Factor in Intestinal Epithelial Cells and Mouse Intestinal Epithelia Reduces Expression of the Chloride Transporter SLC26A3. Gastroenterology. 2017;153(5):1338–50 e3. doi:10.1053/j.gastro.2017.08.024. PMID: 28823863.
   PubMed Web of Science ®Google Scholar
• Cross RK, Wilson KT. Nitric oxide in inflammatory bowel disease. Inflammatory bowel diseases. 2003;9(3):179–89. PMID: 12792224.
   PubMed Web of Science ®Google Scholar
• Zhu H, Li YR. Oxidative stress and redox signaling mechanisms of inflammatory bowel disease: updated experimental and clinical evidence. Exp Biol Med. 2012;237(5):474–80. doi:10.1258/ebm.2011.011358. PMID: 22442342.
   PubMed Web of Science ®Google Scholar
• Kolios G, Valatas V, Ward SG. Nitric oxide in inflammatory bowel disease: a universal messenger in an unsolved puzzle. Immunology. 2004;113(4):427–37. doi:10.1111/j.1365-2567.2004.01984.x. PMID: 15554920.
   PubMed Web of Science ®Google Scholar
• Saksena S, Gill RK, Tyagi S, Alrefai WA, Ramaswamy K, Dudeja PK. Role of Fyn and PI3K in H2O2-induced inhibition of apical Cl-/OH- exchange activity in human intestinal epithelial cells. Biochem J. 2008;416(1):99–108. PMID: 18564062.
   PubMedGoogle Scholar
• Saksena S, Gill RK, Syed IA, Tyagi S, Alrefai WA, Ramaswamy K, Dudeja PK. Modulation of Cl-/OH- exchange activity in Caco-2 cells by nitric oxide. Am J Physiol Gastrointest Liver Physiol. 2002;283(3):G626–33. PMID: 12181176.
   PubMed Web of Science ®Google Scholar
• Odenwald MA, Turner JR. The intestinal epithelial barrier: a therapeutic target? Nature reviews Gastroenterology & hepatology. 2017;14(1):9–21. doi:10.1038/nrgastro.2016.169.
   Google Scholar
• Bischoff SC, Barbara G, Buurman W, Ockhuizen T, Schulzke JD, Serino M, Tilg H, Watson A, Wells JM. Intestinal permeability–a new target for disease prevention and therapy. BMC Gastroenterol. 2014;14:189. doi:10.1186/s12876-014-0189-7.
   PubMed Web of Science ®Google Scholar
• Camilleri M, Sellin JH, Barrett KE. Pathophysiology, Evaluation, and Management of Chronic Watery Diarrhea. Gastroenterology. 2017;152(3):515–32 e2. doi:10.1053/j.gastro.2016.10.014. PMID: 27773805.
   PubMed Web of Science ®Google Scholar
• France MM, Turner JR. The mucosal barrier at a glance. J Cell Sci. 2017;130(2):307–14. doi:10.1242/jcs.193482. PMID: 28062847.
   PubMed Web of Science ®Google Scholar
• Choi W, Yeruva S, Turner JR. Contributions of intestinal epithelial barriers to health and disease. Exp Cell Res. 2017;358(1):71–7. doi:10.1016/j.yexcr.2017.03.036. PMID: 28342899.
   PubMed Web of Science ®Google Scholar
• Barmeyer C, Fromm M, Schulzke JD. Active and passive involvement of claudins in the pathophysiology of intestinal inflammatory diseases. Pflugers Archiv: European journal of physiology. 2017;469(1):15–26. doi:10.1007/s00424-016-1914-6. PMID: 27904960.
   PubMed Web of Science ®Google Scholar
• Lechuga S, Ivanov AI. Disruption of the epithelial barrier during intestinal inflammation: Quest for new molecules and mechanisms. Biochim Biophys Acta. 2017;1864(7):1183–94. doi:10.1016/j.bbamcr.2017.03.007. PMID: 28322932.
   PubMed Web of Science ®Google Scholar
• Lee SH. Intestinal permeability regulation by tight junction: implication on inflammatory bowel diseases. Intestinal research. 2015;13(1):11–8. doi:10.5217/ir.2015.13.1.11. PMID: 25691839.
   PubMed Web of Science ®Google Scholar
• Schulzke JD, Ploeger S, Amasheh M, Fromm A, Zeissig S, Troeger H, Richter J, Bojarski C, Schumann M, Fromm M. Epithelial tight junctions in intestinal inflammation. Ann N Y Acad Sci. 2009;1165:294–300. doi:10.1111/j.1749-6632.2009.04062.x.
   Web of Science ®Google Scholar
• Salim SY, Soderholm JD. Importance of disrupted intestinal barrier in inflammatory bowel diseases. Inflamm Bowel Dis. 2011;17(1):362–81. doi:10.1002/ibd.21403. PMID: 20725949.
   PubMed Web of Science ®Google Scholar
• Van Itallie CM, Anderson JM. Architecture of tight junctions and principles of molecular composition. Semin Cell Dev Biol. 2014;36:157–65. doi:10.1016/j.semcdb.2014.08.011.
   PubMed Web of Science ®Google Scholar
• Mankertz J, Schulzke JD. Altered permeability in inflammatory bowel disease: pathophysiology and clinical implications. Curr Opin Gastroenterol. 2007;23(4):379–83. doi:10.1097/MOG.0b013e32816aa392. PMID: 17545772.
   PubMed Web of Science ®Google Scholar
• Chang J, Leong RW, Wasinger VC, Ip M, Yang M, Phan TG. Impaired Intestinal Permeability Contributes to Ongoing Bowel Symptoms in Patients With Inflammatory Bowel Disease and Mucosal Healing. Gastroenterology. 2017;153(3):723–31 e1. doi:10.1053/j.gastro.2017.05.056. PMID: 28601482.
   PubMed Web of Science ®Google Scholar
• Pastorelli L, De Salvo C, Mercado JR, Vecchi M, Pizarro TT. Central role of the gut epithelial barrier in the pathogenesis of chronic intestinal inflammation: lessons learned from animal models and human genetics. Front Immunol. 2013;4:280. doi:10.3389/fimmu.2013.00280.
   PubMed Web of Science ®Google Scholar
• Ahmad R, Sorrell MF, Batra SK, Dhawan P, Singh AB. Gut permeability and mucosal inflammation: bad, good or context dependent. Mucosal immunology. 2017;10(2):307–17. doi:10.1038/mi.2016.128. PMID: 28120842.
   PubMed Web of Science ®Google Scholar
• Martini E, Krug SM, Siegmund B, Neurath MF, Becker C. Mend Your Fences: The Epithelial Barrier and its Relationship With Mucosal Immunity in Inflammatory Bowel Disease. Cell Mol Gastroenterol Hepatol. 2017;4(1):33–46. doi:10.1016/j.jcmgh.2017.03.007. PMID: 28560287.
   PubMed Web of Science ®Google Scholar
• Zeissig S, Burgel N, Gunzel D, Richter J, Mankertz J, Wahnschaffe U, Kroesen AJ, Zeitz M, Fromm M, Schulzke JD. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Gut. 2007;56(1):61–72. doi:10.1136/gut.2006.094375. PMID: 16822808.
   PubMed Web of Science ®Google Scholar
• Kucharzik T, Walsh SV, Chen J, Parkos CA, Nusrat A. Neutrophil transmigration in inflammatory bowel disease is associated with differential expression of epithelial intercellular junction proteins. Am J Pathol. 2001;159(6):2001–9. doi:10.1016/S0002-9440(10)63051-9. PMID: 11733350.
   PubMed Web of Science ®Google Scholar
• Hering NA, Fromm M, Schulzke JD. Determinants of colonic barrier function in inflammatory bowel disease and potential therapeutics. J Physiol. 2012;590(5):1035–44. doi:10.1113/jphysiol.2011.224568. PMID: 22219336.
   PubMed Web of Science ®Google Scholar
• Vetrano S, Rescigno M, Cera MR, Correale C, Rumio C, Doni A, Fantini M, Sturm A, Borroni E, Repici A, et al. Unique role of junctional adhesion molecule-a in maintaining mucosal homeostasis in inflammatory bowel disease. Gastroenterology. 2008;135(1):173–84. doi:10.1053/j.gastro.2008.04.002. PMID: 18514073.
   PubMed Web of Science ®Google Scholar
• Boivin MA, Roy PK, Bradley A, Kennedy JC, Rihani T, Ma TY. Mechanism of interferon-gamma-induced increase in T84 intestinal epithelial tight junction. Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research. 2009;29(1):45–54. doi:10.1089/jir.2008.0128.
   PubMed Web of Science ®Google Scholar
• Chapman CG, Pekow J. The emerging role of miRNAs in inflammatory bowel disease: a review. Ther Adv Gastroenterol. 2015;8(1):4–22. doi:10.1177/1756283X14547360. PMID: 25553076.
   PubMed Web of Science ®Google Scholar
• Kuang Q, Purhonen P, Hebert H. Structure of potassium channels. Cell Mol Life Sci. 2015;72(19): 3677–93. doi:10.1007/s00018-015-1948-5. Epub 2015 Jun 13. PMID: 26070303.
   PubMed Web of Science ®Google Scholar