The blood–brain and gut–vascular barriers: from the perspective of claudins

References

• Liddelow SA. Fluids and barriers of the CNS: a historical viewpoint. Fluids Barriers CNS. 2011;8(1):1. doi:https://doi.org/10.1186/2045-8118-8-2.
   PubMedGoogle Scholar
• Reese TS, Karnovsky MJ. Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol. 1967;34(1):207–28. doi:https://doi.org/10.1083/jcb.34.1.207.
   PubMed Web of Science ®Google Scholar
• Kalucka J, De Rooij LPMH, Goveia J, Rohlenova K, Dumas SJ, Meta E, Conchinha NV, Taverna F, Teuwen L-A, Veys K, et al. Single-cell transcriptome atlas of murine endothelial cells. Cell. 2020;180(4):764–779 e720. doi:https://doi.org/10.1016/j.cell.2020.01.015.
   PubMed Web of Science ®Google Scholar
• He L, Vanlandewijck M, Mäe MA, Andrae J, Ando K, Del Gaudio F, Nahar K, Lebouvier T, Laviña B, Gouveia L, et al. Single-cell RNA sequencing of mouse brain and lung vascular and vessel-associated cell types. Sci Data. 2018;5(1):180160. doi:https://doi.org/10.1038/sdata.2018.160.
   PubMedGoogle Scholar
• Vanlandewijck M, He L, Mäe MA, Andrae J, Ando K, Del Gaudio F, Nahar K, Lebouvier T, Laviña B, Gouveia L, et al. A molecular atlas of cell types and zonation in the brain vasculature. Nature. 2018;554(7693):475–480. doi:https://doi.org/10.1038/nature25739.
   PubMed Web of Science ®Google Scholar
• Castro Dias M, Mapunda JA, Vladymyrov M, Engelhardt B. Structure and junctional complexes of endothelial, epithelial and glial brain barriers. Int J Mol Sci. 2019;20(21):5372. doi:https://doi.org/10.3390/ijms20215372.
   PubMed Web of Science ®Google Scholar
• Birbrair A. Pericyte biology: development, homeostasis, and disease. Adv Exp Med Biol. 2018;1109:1–3.
   PubMed Web of Science ®Google Scholar
• Spadoni I, Pietrelli A, Pesole G, Rescigno M. Gene expression profile of endothelial cells during perturbation of the gut vascular barrier. Gut Microbes. 2016;7(6):540–548. doi:https://doi.org/10.1080/19490976.2016.1239681.
   PubMed Web of Science ®Google Scholar
• Spadoni I, Zagato E, Bertocchi A, Paolinelli R, Hot E, Di Sabatino A, Caprioli F, Bottiglieri L, Oldani A, Viale G, et al. A gut-vascular barrier controls the systemic dissemination of bacteria. Science. 2015;350(6262):830–834. doi:https://doi.org/10.1126/science.aad0135.
   PubMed Web of Science ®Google Scholar
• Allam-Ndoul B, Castonguay-Paradis S, Veilleux A. Gut microbiota and intestinal trans-epithelial permeability. Int J Mol Sci. 2020;21(17):6402. doi:https://doi.org/10.3390/ijms21176402.
   PubMed Web of Science ®Google Scholar
• Farre R, Fiorani M, Abdu Rahiman S, Matteoli G. Intestinal permeability, inflammation and the role of nutrients. Nutrients. 2020;12(4):1185. doi:https://doi.org/10.3390/nu12041185.
   PubMed Web of Science ®Google Scholar
• Gentile ME, King IL, Knoll LJ. Blood and guts: the intestinal vasculature during health and helminth infection. PLoS Pathog. 2018;14(7):e1007045. doi:https://doi.org/10.1371/journal.ppat.1007045.
   PubMed Web of Science ®Google Scholar
• Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci. 2006;7(1):41–53. doi:https://doi.org/10.1038/nrn1824.
   PubMed Web of Science ®Google Scholar
• Bechmann I, Galea I, Perry VH. What is the blood-brain barrier (not)? Trends Immunol. 2007;28(1):5–11. doi:https://doi.org/10.1016/j.it.2006.11.007.
   PubMed Web of Science ®Google Scholar
• Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis. 2010;37(1):13–25. doi:https://doi.org/10.1016/j.nbd.2009.07.030.
   PubMed Web of Science ®Google Scholar
• Serlin Y, Shelef I, Knyazer B, Friedman A. Anatomy and physiology of the blood-brain barrier. Semin Cell Dev Biol. 2015;38:2–6. doi:https://doi.org/10.1016/j.semcdb.2015.01.002.
   PubMed Web of Science ®Google Scholar
• Jiang S, Khan MI, Lu Y, Werstiuk ES, Rathbone MP. Acceleration of blood-brain barrier formation after transplantation of enteric glia into spinal cords of rats. Exp Brain Res. 2005;162(1):56–62. doi:https://doi.org/10.1007/s00221-004-2119-3.
   PubMed Web of Science ®Google Scholar
• Paolinelli R, Corada M, Orsenigo F, Dejana E. The molecular basis of the blood brain barrier differentiation and maintenance. Is it still a mystery? Pharmacol Res. 2011;63(3):165–171. doi:https://doi.org/10.1016/j.phrs.2010.11.012.
   PubMed Web of Science ®Google Scholar
• Wolburg H, Lippoldt A. Tight junctions of the blood-brain barrier: development, composition and regulation. Vascul Pharmacol. 2002;38(6):323–337. doi:https://doi.org/10.1016/S1537-1891(02)00200-8.
   PubMed Web of Science ®Google Scholar
• Wolburg H, Noell S, Mack A, Wolburg-Buchholz K, Fallier-Becker P. Brain endothelial cells and the glio-vascular complex. Cell Tissue Res. 2009;335(1):75–96. doi:https://doi.org/10.1007/s00441-008-0658-9.
   PubMed Web of Science ®Google Scholar
• Butt AM, Jones HC, Abbott NJ. Electrical resistance across the blood-brain barrier in anaesthetized rats: a developmental study. J Physiol. 1990;429(1):47–62. doi:https://doi.org/10.1113/jphysiol.1990.sp018243.
   PubMedGoogle Scholar
• Crone C, Christensen O. Electrical resistance of a capillary endothelium. J Gen Physiol. 1981;77(4):349–371. doi:https://doi.org/10.1085/jgp.77.4.349.
   PubMed Web of Science ®Google Scholar
• Lv J, Hu W, Yang Z, Li T, Jiang S, Ma Z, Chen F, Yang Y. Focusing on claudin-5: a promising candidate in the regulation of BBB to treat ischemic stroke. Prog Neurobiol. 2018;161:79–96. doi:https://doi.org/10.1016/j.pneurobio.2017.12.001.
   PubMed Web of Science ®Google Scholar
• Wang L, Li Z, Zhang X, Wang S, Zhu C, Miao J, Chen L, Cui L, Qiao H. Protective effect of shikonin in experimental ischemic stroke: attenuated TLR4, p-p38MAPK, NF-κB, TNF-α and MMP-9 expression, up-regulated claudin-5 expression, ameliorated BBB permeability. Neurochem Res. 2014;39(1):97–106. doi:https://doi.org/10.1007/s11064-013-1194-x.
   PubMed Web of Science ®Google Scholar
• Reinhold AK, Rittner HL. Barrier function in the peripheral and central nervous system-a review. Pflugers Arch. 2017;469(1):123–134. doi:https://doi.org/10.1007/s00424-016-1920-8.
   PubMed Web of Science ®Google Scholar
• Goncalves A, Ambrosio AF, Fernandes R. Regulation of claudins in blood-tissue barriers under physiological and pathological states. Tissue Barriers. 2013;1(3):e24782. doi:https://doi.org/10.4161/tisb.24782.
   PubMedGoogle Scholar
• Turksen K, Troy TC. Barriers built on claudins. J Cell Sci. 2004;117(12):2435–2447. doi:https://doi.org/10.1242/jcs.01235.
   PubMed Web of Science ®Google Scholar
• Nagatake T, Zhao Y-C, Ito T, Itoh M, Kometani K, Furuse M, Saika A, Node E, Kunisawa J, Minato N, et al. Selective expression of claudin-5 in thymic endothelial cells regulates the blood-thymus barrier and T-cell export. Int Immunol. 2021;33(3):171–182. doi:https://doi.org/10.1093/intimm/dxaa069.
   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(7):1539–1550. doi:https://doi.org/10.1083/jcb.141.7.1539.
   PubMed Web of Science ®Google Scholar
• Furuse M, Tsukita S. Claudins in occluding junctions of humans and flies. Trends Cell Biol. 2006;16(4):181–188. doi:https://doi.org/10.1016/j.tcb.2006.02.006.
   PubMed Web of Science ®Google Scholar
• Amasheh S, Meiri N, Gitter AH, Schöneberg T, Mankertz J, Schulzke JD, Fromm M. Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells. J Cell Sci. 2002;115(24):4969–4976. doi:https://doi.org/10.1242/jcs.00165.
   PubMed Web of Science ®Google Scholar
• Rosenthal R, Milatz S, Krug SM, Oelrich B, Schulzke J-D, Amasheh S, Günzel D, Fromm M. Claudin-2, a component of the tight junction, forms a paracellular water channel. J Cell Sci. 2010;123(11):1913–1921. doi:https://doi.org/10.1242/jcs.060665.
   PubMed Web of Science ®Google Scholar
• Alexandre MD, Lu Q, Chen Y-H. Overexpression of claudin-7 decreases the paracellular Cl– conductance and increases the paracellular <sup>Na+ conductance in LLC-PK1 cells. J Cell Sci. 2005;118(12):2683–2693. doi:https://doi.org/10.1242/jcs.02406.
   PubMed Web of Science ®Google Scholar
• Colegio OR, Van Itallie CM, McCrea HJ, Rahner C, Anderson JM. Claudins create charge-selective channels in the paracellular pathway between epithelial cells. Am J Physiol Cell Physiol. 2002;283(1):C142–147. doi:https://doi.org/10.1152/ajpcell.00038.2002.
   PubMed Web of Science ®Google Scholar
• Fujita H, Sugimoto K, Inatomi S, Maeda T, Osanai M, Uchiyama Y, Yamamoto Y, Wada T, Kojima T, Yokozaki H, et al. Tight Junction Proteins Claudin-2 and −12 Are Critical for Vitamin D-dependent Ca2+Absorption between Enterocytes. Mol Biol Cell. 2008;19(5):1912–1921. doi:https://doi.org/10.1091/mbc.e07-09-0973.
   PubMed Web of Science ®Google Scholar
• Furuse M, Hata M, Furuse K, Yoshida Y, Haratake A, Sugitani Y, Noda T, Kubo A, Tsukita S. Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J Cell Biol. 2002;156(6):1099–1111. doi:https://doi.org/10.1083/jcb.200110122.
   PubMed Web of Science ®Google Scholar
• Nitta T, Hata M, Gotoh S, Seo Y, Sasaki H, Hashimoto N, Furuse M, Tsukita S. Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J Cell Biol. 2003;161(3):653–660. doi:https://doi.org/10.1083/jcb.200302070.
   PubMed Web of Science ®Google Scholar
• Piontek J, Fritzsche S, Cording J, Richter S, Hartwig J, Walter M, Yu D, Turner JR, Gehring C, Rahn H-P, et al. Elucidating the principles of the molecular organization of heteropolymeric tight junction strands. Cell Mol Life Sci. 2011;68(23):3903–3918. doi:https://doi.org/10.1007/s00018-011-0680-z.
   PubMed Web of Science ®Google Scholar
• Coyne CB, Gambling TM, Boucher RC, Carson JL, Johnson LG. Role of claudin interactions in airway tight junctional permeability. Am J Physiol Lung Cell Mol Physiol. 2003;285(5):L1166–1178. doi:https://doi.org/10.1152/ajplung.00182.2003.
   PubMed Web of Science ®Google Scholar
• Rajagopal N, Irudayanathan FJ, Nangia S. Computational Nanoscopy of Tight Junctions at the Blood-Brain Barrier Interface. Int J Mol Sci. 2019;20(22):5583. doi:https://doi.org/10.3390/ijms20225583.
   Web of Science ®Google Scholar
• Fisher D, Mentor S. Are claudin-5 tight junction proteins in the blood-brain barrier porous? Neural Regen Res. 2020;15(10):1838–1839. doi:https://doi.org/10.4103/1673-5374.280308.
   PubMed Web of Science ®Google Scholar
• Barmeyer C, Schulzke JD, Fromm M. Claudin-related intestinal diseases. Semin Cell Dev Biol. 2015;42:30–38. doi:https://doi.org/10.1016/j.semcdb.2015.05.006.
   PubMed Web of Science ®Google Scholar
• Tsukita S, Yamazaki Y, Katsuno T, Tamura A, Tsukita S. Tight junction-based epithelial microenvironment and cell proliferation. Oncogene. 2008;27(55):6930–6938. doi:https://doi.org/10.1038/onc.2008.344.
   PubMed Web of Science ®Google Scholar
• Rahner C, Mitic LL, Anderson JM. Heterogeneity in expression and subcellular localization of claudins 2, 3, 4, and 5 in the rat liver, pancreas, and gut. Gastroenterology. 2001;120(2):411–422. doi:https://doi.org/10.1053/gast.2001.21736.
   PubMed Web of Science ®Google Scholar
• Shen L, Weber CR, Turner JR. The tight junction protein complex undergoes rapid and continuous molecular remodeling at steady state. J Cell Biol. 2008;181(4):683–695. doi:https://doi.org/10.1083/jcb.200711165.
   PubMed Web of Science ®Google Scholar
• Iwamoto DV, Calderwood DA. Regulation of integrin-mediated adhesions. Curr Opin Cell Biol. 2015;36:41–47. doi:https://doi.org/10.1016/j.ceb.2015.06.009.
   PubMed Web of Science ®Google Scholar
• Lameris AL, Huybers S, Kaukinen K, Mäkelä TH, Bindels RJ, Hoenderop JG, Nevalainen PI. Expression profiling of claudins in the human gastrointestinal tract in health and during inflammatory bowel disease. Scand J Gastroenterol. 2013;48(1):58–69. doi:https://doi.org/10.3109/00365521.2012.741616.
   PubMed Web of Science ®Google Scholar
• Bertiaux-Vandaele N, Youmba SB, Belmonte L, Lecleire S, Antonietti M, Gourcerol G, Leroi A-M, Déchelotte P, Ménard J-F, Ducrotté P, et al. The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype. Am J Gastroenterol. 2011;106(12):2165–2173. doi:https://doi.org/10.1038/ajg.2011.257.
   PubMed Web of Science ®Google Scholar
• Oshima T, Miwa H, Joh T. Changes in the expression of claudins in active ulcerative colitis. J Gastroenterol Hepatol. 2008;23(Suppl 2):S146–150. doi:https://doi.org/10.1111/j.1440-1746.2008.05405.x.
   PubMed Web of Science ®Google Scholar
• Ding L, Lu Z, Foreman O, Tatum R, Lu Q, Renegar R, Cao J, Chen Y. Inflammation and disruption of the mucosal architecture in claudin-7-deficient mice. Gastroenterology. 2012;142(2):305–315. doi:https://doi.org/10.1053/j.gastro.2011.10.025.
   PubMed Web of Science ®Google Scholar
• Fujita H, Chiba H, Yokozaki H, Sakai N, Sugimoto K, Wada T, Kojima T, Yamashita T, Sawada N. Differential expression and subcellular localization of claudin-7, −8, −12, −13, and −15 along the mouse intestine. J Histochem Cytochem. 2006;54(8):933–944. doi:https://doi.org/10.1369/jhc.6A6944.2006.
   PubMed Web of Science ®Google Scholar
• Hagen SJ. Non-canonical functions of claudin proteins: beyond the regulation of cell-cell adhesions. Tissue Barriers. 2017;5(2):e1327839. doi:https://doi.org/10.1080/21688370.2017.1327839.
   PubMed Web of Science ®Google Scholar
• Dhawan P, Singh AB, Deane NG, No Y, Shiou S-R, Schmidt C, Neff J, Washington MK, Beauchamp RD. Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer. J Clin Invest. 2005;115(7):1765–1776. doi:https://doi.org/10.1172/JCI24543.
   Google Scholar
• French AD, Fiori JL, Camilli TC, Leotlela PD, O’Connell MP, Frank BP, Subaran S, Indig FE, Taub DD, Weeraratna AT, et al. PKC and PKA phosphorylation affect the subcellular localization of claudin-1 in melanoma cells. Int J Med Sci. 2009;6:93–101. doi:https://doi.org/10.7150/ijms.6.93.
   PubMed Web of Science ®Google Scholar
• Zwanziger D, Badziong J, Ting S, Moeller LC, Schmid KW, Siebolts U, Wickenhauser C, Dralle H, Fuehrer D. The impact of CLAUDIN-1 on follicular thyroid carcinoma aggressiveness. Endocr Relat Cancer. 2015;22(5):819–830. doi:https://doi.org/10.1530/ERC-14-0502.
   PubMed Web of Science ®Google Scholar
• Ikari A, Watanabe R, Sato T, Taga S, Shimobaba S, Yamaguchi M, Yamazaki Y, Endo S, Matsunaga T, Sugatani J, et al. Nuclear distribution of claudin-2 increases cell proliferation in human lung adenocarcinoma cells. Biochim Biophys Acta. 2014;1843(9):2079–2088. doi:https://doi.org/10.1016/j.bbamcr.2014.05.017.
   PubMed Web of Science ®Google Scholar
• Todd MC, Petty HM, King JM, Piana Marshall BN, Sheller RA, Cuevas ME. Overexpression and delocalization of claudin-3 protein in MCF-7 and MDA-MB-415 breast cancer cell lines. Oncol Lett. 2015;10(1):156–162. doi:https://doi.org/10.3892/ol.2015.3160.
   PubMed Web of Science ®Google Scholar
• Cuevas ME, Gaska JM, Gist AC, King JM, Sheller RA, Todd MC. Estrogen-dependent expression and subcellular localization of the tight junction protein claudin-4 in HEC-1A endometrial cancer cells. Int J Oncol. 2015;47(2):650–656. doi:https://doi.org/10.3892/ijo.2015.3030.
   PubMed Web of Science ®Google Scholar
• Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol. 2001;2(4):285–293. doi:https://doi.org/10.1038/35067088.
   PubMed Web of Science ®Google Scholar
• Ruffer C, Gerke V. The C-terminal cytoplasmic tail of claudins 1 and 5 but not its PDZ-binding motif is required for apical localization at epithelial and endothelial tight junctions. Eur J Cell Biol. 2004;83(4):135–144. doi:https://doi.org/10.1078/0171-9335-00366.
   PubMed Web of Science ®Google Scholar
• Arabzadeh A, Troy TC, Turksen K. Role of the Cldn6 cytoplasmic tail domain in membrane targeting and epidermal differentiation in vivo. Mol Cell Biol. 2006;26(15):5876–5887. doi:https://doi.org/10.1128/MCB.02342-05.
   PubMed Web of Science ®Google Scholar
• Lal-Nag M, Morin PJ. The claudins. Genome Biol. 2009;10(8):235. doi:https://doi.org/10.1186/gb-2009-10-8-235.
   PubMed Web of Science ®Google Scholar
• Gunzel D, Yu AS. Claudins and the modulation of tight junction permeability. Physiol Rev. 2013;93(2):525–569. doi:https://doi.org/10.1152/physrev.00019.2012.
   PubMed Web of Science ®Google Scholar
• Ishizaki T, Chiba H, Kojima T, Fujibe M, Soma T, Miyajima H, Nagasawa K, Wada I, Sawada N. Cyclic AMP induces phosphorylation of claudin-5 immunoprecipitates and expression of claudin-5 gene in blood-brain-barrier endothelial cells via protein kinase A-dependent and -independent pathways. Exp Cell Res. 2003;290(2):275–288. doi:https://doi.org/10.1016/S0014-4827(03)00354-9.
   PubMed Web of Science ®Google Scholar
• Soma T, Chiba H, Kato-Mori Y, Wada T, Yamashita T, Kojima T, Sawada N. Thr(207) of claudin-5 is involved in size-selective loosening of the endothelial barrier by cyclic AMP. Exp Cell Res. 2004;300(1):202–212. doi:https://doi.org/10.1016/j.yexcr.2004.07.012.
   PubMed Web of Science ®Google Scholar
• Persidsky Y, Heilman D, Haorah J, Zelivyanskaya M, Persidsky R, Weber GA, Shimokawa H, Kaibuchi K, Ikezu T. Rho-mediated regulation of tight junctions during monocyte migration across the blood-brain barrier in HIV-1 encephalitis (HIVE). Blood. 2006;107(12):4770–4780. doi:https://doi.org/10.1182/blood-2005-11-4721.
   PubMed Web of Science ®Google Scholar
• Fujibe M, Chiba H, Kojima T, Soma T, Wada T, Yamashita T, Sawada N. Thr203 of claudin-1, a putative phosphorylation site for MAP kinase, is required to promote the barrier function of tight junctions. Exp Cell Res. 2004;295(1):36–47. doi:https://doi.org/10.1016/j.yexcr.2003.12.014.
   PubMed Web of Science ®Google Scholar
• Van Itallie CM, Gambling TM, Carson JL, Anderson JM. Palmitoylation of claudins is required for efficient tight junction localization. J Cell Sci. 2005;118(7):1427–1436. doi:https://doi.org/10.1242/jcs.01735.
   PubMed Web of Science ®Google Scholar
• Chau V, Tobias J, Bachmair A, Marriott D, Ecker D, Gonda D, Varshavsky A. A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science. 1989;243(4898):1576–1583. doi:https://doi.org/10.1126/science.2538923.
   PubMed Web of Science ®Google Scholar
• Kerscher O, Felberbaum R, Hochstrasser M. Modification of proteins by ubiquitin and ubiquitin-like proteins. Annu Rev Cell Dev Biol. 2006;22(1):159–180. doi:https://doi.org/10.1146/annurev.cellbio.22.010605.093503.
   PubMedGoogle Scholar
• Takahashi S, Iwamoto N, Sasaki H, Ohashi M, Oda Y, Tsukita S, Furuse M. The E3 ubiquitin ligase LNX1p80 promotes the removal of claudins from tight junctions in MDCK cells. J Cell Sci. 2009;122(7):985–994. doi:https://doi.org/10.1242/jcs.040055.
   PubMed Web of Science ®Google Scholar
• Itoh M, Furuse M, Morita K, Kubota K, Saitou M, Tsukita S. Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. J Cell Biol. 1999;147(6):1351–1363. doi:https://doi.org/10.1083/jcb.147.6.1351.
   PubMed Web of Science ®Google Scholar
• Hamazaki Y, Itoh M, Sasaki H, Furuse M, Tsukita S. Multi-PDZ domain protein 1 (MUPP1) is concentrated at tight junctions through its possible interaction with claudin-1 and junctional adhesion molecule. J Biol Chem. 2002;277(1):455–461. doi:https://doi.org/10.1074/jbc.M109005200.
   PubMed Web of Science ®Google Scholar
• Roh MH, Liu CJ, Laurinec S, Margolis B. The carboxyl terminus of zona occludens-3 binds and recruits a mammalian homologue of discs lost to tight junctions. J Biol Chem. 2002;277(30):27501–27509. doi:https://doi.org/10.1074/jbc.M201177200.
   PubMed Web of Science ®Google Scholar
• Colegio OR, Van Itallie C, Rahner C, Anderson JM. Claudin extracellular domains determine paracellular charge selectivity and resistance but not tight junction fibril architecture. Am J Physiol Cell Physiol. 2003;284(6):C1346–1354. doi:https://doi.org/10.1152/ajpcell.00547.2002.
   PubMed Web of Science ®Google Scholar
• Blasig IE, Winkler L, Lassowski B, Mueller SL, Zuleger N, Krause E, Krause G, Gast K, Kolbe M, Piontek J, et al. On the self-association potential of transmembrane tight junction proteins. Cell Mol Life Sci. 2006;63(4):505–514. doi:https://doi.org/10.1007/s00018-005-5472-x.
   PubMed Web of Science ®Google Scholar
• Piontek J, Winkler L, Wolburg H, Müller SL, Zuleger N, Piehl C, Wiesner B, Krause G, Blasig IE. Formation of tight junction: determinants of homophilic interaction between classic claudins. FASEB J. 2008;22(1):146–158. doi:https://doi.org/10.1096/fj.07-8319com.
   PubMed Web of Science ®Google Scholar
• Van Itallie CM, Mitic LL, Anderson JM. Claudin-2 forms homodimers and is a component of a high molecular weight protein complex. J Biol Chem. 2011;286(5):3442–3450. doi:https://doi.org/10.1074/jbc.M110.195578.
   PubMed Web of Science ®Google Scholar
• Fujita K, Katahira J, Horiguchi Y, Sonoda N, Furuse M, Tsukita S. Clostridium perfringens enterotoxin binds to the second extracellular loop of claudin-3, a tight junction integral membrane protein. FEBS Lett. 2000;476(3):258–261. doi:https://doi.org/10.1016/S0014-5793(00)01744-0.
   PubMed Web of Science ®Google Scholar
• Katahira J, Sugiyama H, Inoue N, Horiguchi Y, Matsuda M, Sugimoto N. Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo. J Biol Chem. 1997;272(42):26652–26658. doi:https://doi.org/10.1074/jbc.272.42.26652.
   PubMed Web of Science ®Google Scholar
• Hanna PC, Mietzner TA, Schoolnik GK, McClane BA. Localization of the receptor-binding region of Clostridium perfringens enterotoxin utilizing cloned toxin fragments and synthetic peptides. The 30 C-terminal amino acids define a functional binding region. J Biol Chem. 1991;266(17):11037–11043. doi:https://doi.org/10.1016/S0021-9258(18)99124-6.
   PubMed Web of Science ®Google Scholar
• Sonoda N, Furuse M, Sasaki H, Yonemura S, Katahira J, Horiguchi Y, Tsukita S. Clostridium perfringens enterotoxin fragment removes specific claudins from tight junction strands: evidence for direct involvement of claudins in tight junction barrier. J Cell Biol. 1999;147(1):195–204. doi:https://doi.org/10.1083/jcb.147.1.195.
   PubMed Web of Science ®Google Scholar
• Kreczmanski P, Heinsen H, Mantua V, Woltersdorf F, Masson T, Ulfig N, Schmidt-Kastner R, Korr H, Steinbusch HWM, Hof PR, et al. Microvessel length density, total length, and length per neuron in five subcortical regions in schizophrenia. Acta Neuropathol. 2009;117(4):409–421. doi:https://doi.org/10.1007/s00401-009-0482-7.
   PubMed Web of Science ®Google Scholar
• Morita K, Sasaki H, Furuse M, Tsukita S. Endothelial claudin: claudin-5/TMVCF constitutes tight junction strands in endothelial cells. J Cell Biol. 1999;147(1):185–194. doi:https://doi.org/10.1083/jcb.147.1.185.
   PubMed Web of Science ®Google Scholar
• Liebner S, Kniesel U, Kalbacher H, Wolburg H. Correlation of tight junction morphology with the expression of tight junction proteins in blood-brain barrier endothelial cells. Eur J Cell Biol. 2000;79(10):707–717. doi:https://doi.org/10.1078/0171-9335-00101.
   PubMed Web of Science ®Google Scholar
• Ohtsuki S, Yamaguchi H, Katsukura Y, Asashima T, Terasaki T. mRNA expression levels of tight junction protein genes in mouse brain capillary endothelial cells highly purified by magnetic cell sorting. J Neurochem. 2008;104(1):147–154.doi:https://doi.org/10.1111/j.1471-4159.2007.05008.x.
   PubMed Web of Science ®Google Scholar
• Cooper I, Cohen-Kashi-Malina K, Teichberg VI. Claudin-5 expression in in-vitro models of the blood-brain barrier. Methods Mol Biol. 2011;762:347–354.
   PubMedGoogle Scholar
• Neuhaus W, Wirth M, Plattner VE, Germann B, Gabor F, Noe CR. Expression of claudin-1, claudin-3 and claudin-5 in human blood-brain barrier mimicking cell line ECV304 is inducible by glioma-conditioned media. Neurosci Lett. 2008;446(2–3):59–64. doi:https://doi.org/10.1016/j.neulet.2008.09.025.
   PubMed Web of Science ®Google Scholar
• Campbell M, Kiang A-S, Kenna PF, Kerskens C, Blau C, O’Dwyer L, Tivnan A, Kelly JA, Brankin B, Farrar G-J, et al. RNAi-mediated reversible opening of the blood-brain barrier. J Gene Med. 2008;10(8):930–947. doi:https://doi.org/10.1002/jgm.1211.
   PubMed Web of Science ®Google Scholar
• Kakogiannos N, Ferrari L, Giampietro C, Scalise AA, Maderna C, Ravà M, Taddei A, Lampugnani MG, Pisati F, Malinverno M, et al. JAM-A Acts via C/EBP-α to promote claudin-5 expression and enhance endothelial barrier function. Circ Res. 2020;127(8):1056–1073. doi:https://doi.org/10.1161/CIRCRESAHA.120.316742.
   PubMed Web of Science ®Google Scholar
• Castro Dias M, Coisne C, Baden P, Enzmann G, Garrett L, Becker L, Hölter SM, Hrabě De Angelis M, Deutsch U, Engelhardt B, et al. Claudin-12 is not required for blood–brain barrier tight junction function. Fluids and Barriers of the CNS. 2019;16(1):30. doi:https://doi.org/10.1186/s12987-019-0150-9.
   PubMed Web of Science ®Google Scholar
• Shimizu F, Sano Y, Maeda T, Abe M-A, Nakayama H, Takahashi R-I, Ueda M, Ohtsuki S, Terasaki T, Obinata M, et al. Peripheral nerve pericytes originating from the blood-nerve barrier expresses tight junctional molecules and transporters as barrier-forming cells. J Cell Physiol. 2008;217(2):388–399. doi:https://doi.org/10.1002/jcp.21508.
   PubMed Web of Science ®Google Scholar
• Liebner S, Corada M, Bangsow T, Babbage J, Taddei A, Czupalla CJ, Reis M, Felici A, Wolburg H, Fruttiger M, et al. Wnt/β-catenin signaling controls development of the blood-brain barrier. J Cell Biol. 2008;183(3):409–417. doi:https://doi.org/10.1083/jcb.200806024.
   PubMed Web of Science ®Google Scholar
• Wolburg H, Wolburg-Buchholz K, Kraus J, Rascher-Eggstein G, Liebner S, Hamm S, Duffner F, Grote E-H, Risau W, Engelhardt B, et al. Localization of claudin-3 in tight junctions of the blood-brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme. Acta Neuropathol. 2003;105(6):586–592. doi:https://doi.org/10.1007/s00401-003-0688-z.
   PubMed Web of Science ®Google Scholar
• Berndt P, Winkler L, Cording J, Breitkreuz-Korff O, Rex A, Dithmer S, Rausch V, Blasig R, Richter M, Sporbert A, et al. Tight junction proteins at the blood-brain barrier: far more than claudin-5. Cell Mol Life Sci. 2019;76(10):1987–2002. doi:https://doi.org/10.1007/s00018-019-03030-7.
   PubMed Web of Science ®Google Scholar
• Pardridge WM, Triguero D, Yang J, Cancilla PA. Comparison of in-vitro and in-vivo models of drug transcytosis through the blood-brain barrier. J Pharmacol Exp Ther. 1990;253:884–891.
   PubMed Web of Science ®Google Scholar
• Castro Dias M, Coisne C, Lazarevic I, Baden P, Hata M, Iwamoto N, Francisco DMF, Vanlandewijck M, He L, Baier FA, et al. Claudin-3-deficient C57BL/6J mice display intact brain barriers. Sci Rep. 2019;9(1):203. doi:https://doi.org/10.1038/s41598-018-36731-3.
   PubMedGoogle Scholar
• Kachlik D, Baca V, Stingl J. The spatial arrangement of the human large intestinal wall blood circulation. J Anat. 2010;216(3):335–343. doi:https://doi.org/10.1111/j.1469-7580.2009.01199.x.
   PubMed Web of Science ®Google Scholar
• Granger DN, Holm L, Kvietys P. The gastrointestinal circulation: physiology and pathophysiology. Compr Physiol. 2015;5:1541–1583.
   PubMed Web of Science ®Google Scholar
• Thorburn T, Aali M, Lehmann C, Aali M, Lehmann C, Lehmann C. Immune response to systemic inflammation in the intestinal microcirculation. Front Biosci (Landmark Ed). 2018;23(2):782–795. doi:https://doi.org/10.2741/4616.
   PubMedGoogle Scholar
• Kvietys PR. The Gastrointestinal Circulation. Colloquium Series on Integrated Systems Physiology: From Molecule to Function, San Rafael (CA): Morgan & Claypool Life Sciences, 2010, 2(1): 1–127. https://doi.org/10.4199/C00009ED1V01Y201002ISP005
   Google Scholar
• Spadoni I, Fornasa G, Rescigno M. Organ-specific protection mediated by cooperation between vascular and epithelial barriers. Nat Rev Immunol. 2017;17(12):761–773. doi:https://doi.org/10.1038/nri.2017.100.
   PubMed Web of Science ®Google Scholar
• Lee S, Chen TT, Barber CL, Jordan MC, Murdock J, Desai S, Ferrara N, Nagy A, Roos KP, Iruela-Arispe ML, et al. Autocrine VEGF signaling is required for vascular homeostasis. Cell. 2007;130(4):691–703. doi:https://doi.org/10.1016/j.cell.2007.06.054.
   PubMed Web of Science ®Google Scholar
• Murakami M, Nguyen LT, Zhang ZW, Moodie KL, Carmeliet P, Stan RV, Simons M. The FGF system has a key role in regulating vascular integrity. J Clin Invest. 2008;118(10):3355–3366. doi:https://doi.org/10.1172/JCI35298.
   PubMed Web of Science ®Google Scholar
• Kashiwazaki M, Tanaka T, Kanda H, Ebisuno Y, Izawa D, Fukuma N, Akimitsu N, Sekimizu K, Monden M, Miyasaka M. A high endothelial venule-expressing promiscuous chemokine receptor DARC can bind inflammatory, but not lymphoid, chemokines and is dispensable for lymphocyte homing under physiological conditions. Int Immunol. 2003;15(10):1219–1227. doi:https://doi.org/10.1093/intimm/dxg121.
   PubMed Web of Science ®Google Scholar
• Saito K, Tanaka T, Kanda H, Ebisuno Y, Izawa D, Kawamoto S, Okubo K, Miyasaka M. Gene expression profiling of mucosal addressin cell adhesion molecule-1+ high endothelial venule cells (HEV) and Identification of a Leucine-Rich HEV Glycoprotein as a HEV Marker. J Immunol. 2002;168(3):1050–1059. doi:https://doi.org/10.4049/jimmunol.168.3.1050.
   PubMed Web of Science ®Google Scholar
• Girard JP, Moussion C, Forster R. HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes. Nat Rev Immunol. 2012;12(11):762–773. doi:https://doi.org/10.1038/nri3298.
   PubMed Web of Science ®Google Scholar
• Obermeier B, Daneman R, Ransohoff RM. Development, maintenance and disruption of the blood-brain barrier. Nat Med. 2013;19(12):1584–1596. doi:https://doi.org/10.1038/nm.3407.
   PubMed Web of Science ®Google Scholar
• Alonso AD, Cohen LS, Corbo C, Morozova V, ElIdrissi A, Phillips G, Kleiman FE. Hyperphosphorylation of Tau associates with changes in its function beyond microtubule stability. Front Cell Neurosci. 2018;12:338. doi:https://doi.org/10.3389/fncel.2018.00338.
   PubMed Web of Science ®Google Scholar
• Rao CV, Asch AS, Carr DJJ, Yamada HY. “Amyloid-β accumulation cycle” as a prevention and/or therapy target for Alzheimer’s disease. Aging Cell. 2020;19(3):e13109. doi:https://doi.org/10.1111/acel.13109.
   PubMed Web of Science ®Google Scholar
• Wisniewski HM, Vorbrodt AW, Wegiel J. Amyloid angiopathy and blood-brain barrier changes in Alzheimer’s disease. Ann N Y Acad Sci. 1997;826:161–172. doi:https://doi.org/10.1111/j.1749-6632.1997.tb48468.x.
   PubMed Web of Science ®Google Scholar
• Nation DA, Sweeney MD, Montagne A, Sagare AP, D’Orazio LM, Pachicano M, Sepehrband F, Nelson AR, Buennagel DP, Harrington MG, et al. Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nat Med. 2019;25(2):270–276. doi:https://doi.org/10.1038/s41591-018-0297-y.
   PubMed Web of Science ®Google Scholar
• Carrano A, Hoozemans JJM, Van Der Vies SM, Rozemuller AJM, Van Horssen J, De Vries HE. Amyloid β induces oxidative stress-mediated blood-brain barrier changes in capillary amyloid angiopathy. Antioxid Redox Signal. 2011;15(5):1167–1178. doi:https://doi.org/10.1089/ars.2011.3895.
   PubMed Web of Science ®Google Scholar
• Carrano A, Hoozemans JJM, Van Der Vies SM, Van Horssen J, De Vries HE, Rozemuller AJM. Neuroinflammation and blood-brain barrier changes in capillary amyloid angiopathy. Neurodegener Dis. 2012;10(1–4):329–331. doi:https://doi.org/10.1159/000334916.
   PubMed Web of Science ®Google Scholar
• Viggars AP, Wharton SB, Simpson JE, Matthews FE, Brayne C, Savva GM, Garwood C, Drew D, Shaw PJ, Ince PG, et al. Alterations in the blood brain barrier in ageing cerebral cortex in relationship to Alzheimer-type pathology: a study in the MRC-CFAS population neuropathology cohort. Neurosci Lett. 2011;505(1):25–30. doi:https://doi.org/10.1016/j.neulet.2011.09.049.
   PubMed Web of Science ®Google Scholar
• Ujiie M, Dickstein DL, Carlow DA, Jefferies WA. Blood-brain barrier permeability precedes senile plaque formation in an Alzheimer disease model. Microcirculation. 2003;10(6):463–470. doi:https://doi.org/10.1038/sj.mn.7800212.
   PubMed Web of Science ®Google Scholar
• Winkler EA, Nishida Y, Sagare AP, Rege SV, Bell RD, Perlmutter D, Sengillo JD, Hillman S, Kong P, Nelson AR, et al. GLUT1 reductions exacerbate Alzheimer’s disease vasculo-neuronal dysfunction and degeneration. Nat Neurosci. 2015;18(4):521–530. doi:https://doi.org/10.1038/nn.3966.
   PubMed Web of Science ®Google Scholar
• Hartz AM, Bauer B, Soldner ELB, Wolf A, Boy S, Backhaus R, Mihaljevic I, Bogdahn U, Klünemann HH, Schuierer G, et al. Amyloid-β contributes to blood-brain barrier leakage in transgenic human amyloid precursor protein mice and in humans with cerebral amyloid angiopathy. Stroke. 2012;43(2):514–523. doi:https://doi.org/10.1161/STROKEAHA.111.627562.
   PubMed Web of Science ®Google Scholar
• Keaney J, Walsh DM, O’Malley T, Hudson N, Crosbie DE, Loftus T, Sheehan F, McDaid J, Humphries MM, Callanan JJ, et al. Autoregulated paracellular clearance of amyloid-β across the blood-brain barrier. Sci Adv. 2015;1(8):e1500472. doi:https://doi.org/10.1126/sciadv.1500472.
   PubMed Web of Science ®Google Scholar
• Bien-Ly N, Boswell C, Jeet S, Beach T, Hoyte K, Luk W, Shihadeh V, Ulufatu S, Foreman O, Lu Y, et al. Lack of widespread BBB disruption in Alzheimer’s disease models: focus on therapeutic antibodies. Neuron. 2015;88(2):289–297. doi:https://doi.org/10.1016/j.neuron.2015.09.036.
   PubMed Web of Science ®Google Scholar
• Davis SM, Donnan GA. Clinical practice. Secondary prevention after ischemic stroke or transient ischemic attack. N Engl J Med. 2012;366(20):1914–1922. doi:https://doi.org/10.1056/NEJMcp1107281.
   PubMed Web of Science ®Google Scholar
• Yang C, Hawkins KE, Dore S, Candelario-Jalil E. Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke. Am J Physiol Cell Physiol. 2019;316(2):C135–C153. doi:https://doi.org/10.1152/ajpcell.00136.2018.
   PubMed Web of Science ®Google Scholar
• Knowland D, Arac A, Sekiguchi K, Hsu M, Lutz S, Perrino J, Steinberg G, Barres B, Nimmerjahn A, Agalliu D, et al. Stepwise recruitment of transcellular and paracellular pathways underlies blood-brain barrier breakdown in stroke. Neuron. 2014;82(3):603–617. doi:https://doi.org/10.1016/j.neuron.2014.03.003.
   PubMed Web of Science ®Google Scholar
• Krueger M, Bechmann I, Immig K, Reichenbach A, Härtig W, Michalski D. Blood-brain barrier breakdown involves four distinct stages of vascular damage in various models of experimental focal cerebral ischemia. J Cereb Blood Flow Metab. 2015;35(2):292–303. doi:https://doi.org/10.1038/jcbfm.2014.199.
   PubMed Web of Science ®Google Scholar
• De Bock M, Van Haver V, Vandenbroucke RE, Decrock E, Wang N, Leybaert L. Into rather unexplored terrain-transcellular transport across the blood-brain barrier. Glia. 2016 Jul;64(7):1097–1123. doi: https://doi.org/10.1002/glia.22960.
   Google Scholar
• Willis CL, Meske DS, Davis TP. Protein kinase C activation modulates reversible increase in cortical blood-brain barrier permeability and tight junction protein expression during hypoxia and posthypoxic reoxygenation. J Cereb Blood Flow Metab. 2010;30(11):1847–1859. doi:https://doi.org/10.1038/jcbfm.2010.119.
   PubMed Web of Science ®Google Scholar
• Bauer AT, Burgers HF, Rabie T, Marti HH. Matrix metalloproteinase-9 mediates hypoxia-induced vascular leakage in the brain via tight junction rearrangement. J Cereb Blood Flow Metab. 2010;30(4):837–848. doi:https://doi.org/10.1038/jcbfm.2009.248.
   PubMed Web of Science ®Google Scholar
• Jiao H, Wang Z, Liu Y, Wang P, Xue Y. Specific role of tight junction proteins claudin-5, occludin, and ZO-1 of the blood-brain barrier in a focal cerebral ischemic insult. J Mol Neurosci. 2011;44(2):130–139. doi:https://doi.org/10.1007/s12031-011-9496-4.
   PubMed Web of Science ®Google Scholar
• Liu P, Zhang R, Liu D, Wang J, Yuan C, Zhao X, Li Y, Ji X, Chi T, Zou L, et al. Time-course investigation of blood-brain barrier permeability and tight junction protein changes in a rat model of permanent focal ischemia. J Physiol Sci. 2018;68(2):121–127. doi:https://doi.org/10.1007/s12576-016-0516-6.
   PubMed Web of Science ®Google Scholar
• Winkler L, Blasig R, Breitkreuz-Korff O, Berndt P, Dithmer S, Helms HC, Puchkov D, Devraj K, Kaya M, Qin Z, et al. Tight junctions in the blood-brain barrier promote edema formation and infarct size in stroke - ambivalent effects of sealing proteins. J Cereb Blood Flow Metab. 2021;41(1):132–145. doi:https://doi.org/10.1177/0271678X20904687.
   PubMed Web of Science ®Google Scholar
• Sladojevic N, Stamatovic SM, Johnson AM, Choi J, Hu A, Dithmer S, Blasig IE, Keep RF, Andjelkovic AV. Claudin-1-dependent destabilization of the blood-brain barrier in chronic stroke. J Neurosci. 2019;39:743–757. doi:https://doi.org/10.1523/JNEUROSCI.1432-18.2018.
   PubMed Web of Science ®Google Scholar
• Goldenberg MM. Multiple sclerosis review. P T. 2012;37:175–184.
   PubMedGoogle Scholar
• Kermode AG, Thompson AJ, Tofts P, Macmanus DG, Kendall BE, Kingsley DPE, Moseley IF, Rudge P, Mcdonald WI. Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications. Brain. 1990;113(Pt 5):1477–1489. doi:https://doi.org/10.1093/brain/113.5.1477.
   PubMedGoogle Scholar
• Plumb J, McQuaid S, Mirakhur M, Kirk J. Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis. Brain Pathol. 2002;12(2):154–169. doi:https://doi.org/10.1111/j.1750-3639.2002.tb00430.x.
   PubMed Web of Science ®Google Scholar
• Kirk J, Plumb J, Mirakhur M, McQuaid S. Tight junctional abnormality in multiple sclerosis white matter affects all calibres of vessel and is associated with blood-brain barrier leakage and active demyelination. J Pathol. 2003;201(2):319–327. doi:https://doi.org/10.1002/path.1434.
   PubMed Web of Science ®Google Scholar
• Van Horssen J, Brink BP, De Vries HE, Van Der Valk P, Bo L. The blood-brain barrier in cortical multiple sclerosis lesions. J Neuropathol Exp Neurol. 2007;66(4):321–328. doi:https://doi.org/10.1097/nen.0b013e318040b2de.
   PubMed Web of Science ®Google Scholar
• Errede M, Girolamo F, Ferrara G, Strippoli M, Morando S, Boldrin V, Rizzi M, Uccelli A, Perris R, Bendotti C, et al. Blood-brain barrier alterations in the cerebral cortex in experimental autoimmune encephalomyelitis. J Neuropathol Exp Neurol. 2012;71(10):840–854. doi:https://doi.org/10.1097/NEN.0b013e31826ac110.
   PubMed Web of Science ®Google Scholar
• Wang D, Li S-P, Fu J-S, Zhang S, Bai L, Guo L. Resveratrol defends blood-brain barrier integrity in experimental autoimmune encephalomyelitis mice. J Neurophysiol. 2016;116(5):2173–2179. doi:https://doi.org/10.1152/jn.00510.2016.
   PubMed Web of Science ®Google Scholar
• Huang J, Han S, Sun Q, Zhao Y, Liu J, Yuan X, Mao W, Peng B, Liu W, Yin J, et al. Kv1.3 channel blocker (ImKTx88) maintains blood-brain barrier in experimental autoimmune encephalomyelitis. Cell Biosci. 2017;7(1):31. doi:https://doi.org/10.1186/s13578-017-0158-2.
   PubMedGoogle Scholar
• Uchida Y, Sumiya T, Tachikawa M, Yamakawa T, Murata S, Yagi Y, Sato K, Stephan A, Ito K, Ohtsuki S, et al. Involvement of claudin-11 in disruption of blood-brain, -spinal cord, and -arachnoid barriers in multiple sclerosis. Mol Neurobiol. 2019;56(3):2039–2056. doi:https://doi.org/10.1007/s12035-018-1207-5.
   PubMed Web of Science ®Google Scholar
• Greene C, Hanley N, Campbell M. Blood-brain barrier associated tight junction disruption is a hallmark feature of major psychiatric disorders. Transl Psychiatry. 2020;10(1):373. doi:https://doi.org/10.1038/s41398-020-01054-3.
   PubMed Web of Science ®Google Scholar
• Enwright Iii JF, Huo Z, Arion D, Corradi JP, Tseng G, Lewis DA. Transcriptome alterations of prefrontal cortical parvalbumin neurons in schizophrenia. Mol Psychiatry. 2018;23(7):1606–1613. doi:https://doi.org/10.1038/mp.2017.216.
   PubMed Web of Science ®Google Scholar
• Murphy KC. Schizophrenia and velo-cardio-facial syndrome. Lancet. 2002;359(9304):426–430. doi:https://doi.org/10.1016/S0140-6736(02)07604-3.
   PubMed Web of Science ®Google Scholar
• Williams NM. Molecular mechanisms in 22q11 deletion syndrome. Schizophr Bull. 2011;37(5):882–889. doi:https://doi.org/10.1093/schbul/sbr095.
   PubMed Web of Science ®Google Scholar
• Kao A, Mariani J, McDonald-McGinn DM, Maisenbacher MK, Brooks-Kayal AR, Zackai EH, Lynch DR. Increased prevalence of unprovoked seizures in patients with a 22q11.2 deletion. Am J Med Genet A. 2004;129A(1):29–34. doi:https://doi.org/10.1002/ajmg.a.30133.
   PubMed Web of Science ®Google Scholar
• Greene C, Kealy J, Humphries MM, Gong Y, Hou J, Hudson N, Cassidy LM, Martiniano R, Shashi V, Hooper SR, et al. Dose-dependent expression of claudin-5 is a modifying factor in schizophrenia. Mol Psychiatry. 2018;23(11):2156–2166. doi:https://doi.org/10.1038/mp.2017.156.
   PubMed Web of Science ®Google Scholar
• Nishiura K, Ichikawa-Tomikawa N, Sugimoto K, Kunii Y, Kashiwagi K, Tanaka M, Yokoyama Y, Hino M, Sugino T, Yabe H, et al. PKA activation and endothelial claudin-5 breakdown in the schizophrenic prefrontal cortex. Oncotarget. 2017;8(55):93382–93391. doi:https://doi.org/10.18632/oncotarget.21850.
   PubMedGoogle Scholar
• Maes M, Sirivichayakul S, Kanchanatawan B, Vodjani A. Breakdown of the paracellular tight and adherens junctions in the gut and blood brain barrier and damage to the vascular barrier in patients with deficit schizophrenia. Neurotox Res. 2019;36(2):306–322. doi:https://doi.org/10.1007/s12640-019-00054-6.
   PubMed Web of Science ®Google Scholar
• Groschwitz KR, Hogan SP. Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol. 2009 quiz 21-22;124(1):3–20. doi:https://doi.org/10.1016/j.jaci.2009.05.038.
   PubMed Web of Science ®Google Scholar
• Sorribas M, Jakob MO, Yilmaz B, Li H, Stutz D, Noser Y, De Gottardi A, Moghadamrad S, Hassan M, Albillos A, et al. FXR modulates the gut-vascular barrier by regulating the entry sites for bacterial translocation in experimental cirrhosis. J Hepatol. 2019;71(6):1126–1140. doi:https://doi.org/10.1016/j.jhep.2019.06.017.
   PubMed Web of Science ®Google Scholar
• Cheng C, Tan J, Qian W, Zhang L, Hou X. Gut inflammation exacerbates hepatic injury in the high-fat diet induced NAFLD mouse: attention to the gut-vascular barrier dysfunction. Life Sci. 2018;209:157–166. doi:https://doi.org/10.1016/j.lfs.2018.08.017.
   PubMed Web of Science ®Google Scholar
• Boschetti E, Accarino A, Malagelada C, Malagelada JR, Cogliandro RF, Gori A, Tugnoli V, Giancola F, Bianco F, Bonora E, et al. Gut epithelial and vascular barrier abnormalities in patients with chronic intestinal pseudo-obstruction. Neurogastroenterol Motil. 2019;31(8):e13652. doi:https://doi.org/10.1111/nmo.13652.
   PubMed Web of Science ®Google Scholar
• Luettig J, Rosenthal R, Barmeyer C, Schulzke JD. Claudin-2 as a mediator of leaky gut barrier during intestinal inflammation. Tissue Barriers. 2015;3(1–2):e977176. doi:https://doi.org/10.4161/21688370.2014.977176.
   PubMed Web of Science ®Google Scholar
• Liu P, Bian Y, Fan Y, Zhong J, Liu Z. Protective effect of naringin on in-vitro gut-vascular barrier disruption of intestinal microvascular endothelial cells induced by TNF-α. J Agric Food Chem. 2020;68(1):168–175. doi:https://doi.org/10.1021/acs.jafc.9b06347.
   PubMed Web of Science ®Google Scholar
• He Y, Yuan X, Zuo H, Sun Y, Feng A. Berberine exerts a protective effect on gut-vascular barrier via the modulation of the Wnt/β-catenin signaling pathway during sepsis. Cell Physiol Biochem. 2018;49(4):1342–1351. doi:https://doi.org/10.1159/000493412.
   PubMedGoogle Scholar
• Ciccia F, Guggino G, Rizzo A, Alessandro R, Luchetti MM, Milling S, Saieva L, Cypers H, Stampone T, Di Benedetto P, et al. Dysbiosis and zonulin up-regulation alter gut epithelial and vascular barriers in patients with ankylosing spondylitis. Ann Rheum Dis. 2017;76(6):1123–1132. doi:https://doi.org/10.1136/annrheumdis-2016-210000.
   PubMed Web of Science ®Google Scholar
• Bertocchi A, Carloni S, Ravenda PS, Bertalot G, Spadoni I, Lo Cascio A, Gandini S, Lizier M, Braga D, Asnicar F, et al. Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver. Cancer Cell. 2021. doi:https://doi.org/10.1016/j.ccell.2021.03.004.
   Google Scholar
• Mouries J, Brescia P, Silvestri A, Spadoni I, Sorribas M, Wiest R, Mileti E, Galbiati M, Invernizzi P, Adorini L, et al. Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development. J Hepatol. 2019;71(6):1216–1228. doi:https://doi.org/10.1016/j.jhep.2019.08.005.
   PubMed Web of Science ®Google Scholar