Función de barrera intestinal
Alteración e implicancias en las enfermedades inflamatorias intestinales
DOI:
https://doi.org/10.35305/fcm.v4i.119Palabras clave:
Barrera Intestinal, regulación, implicancias, Enfermedades Inflamatorias IntestinalesResumen
La barrera intestinal cumple un rol importante en la defensa contra toxinas, xenobióticos y moléculas potencialmente dañinas, al tiempo que permite la absorción de nutrientes, electrolitos y agua. Estas funciones son llevadas a cabo por células epiteliales especializadas, en las cuales la permeabilidad selectiva se logra a través de dos vías: paracelular y transcelular. La primera comprende el ingreso de moléculas a través del espacio entre las células, mientras que la vía transcelular implica el movimiento de moléculas a través de las membranas celulares y está mediado por transportadores transmembrana apicales y basolaterales. La desregulación de estas vías está implicada en la patogénesis de las enfermedades inflamatorias intestinales, incluyendo la enfermedad de Crohn y la colitis ulcerosa.
En esta revisión se describen los avances en el conocimiento de los componentes de la barrera intestinal, su regulación y su implicancia en las enfermedades inflamatorias intestinales. Esto es de gran relevancia para comprender los mecanismos involucrados en la fisiopatología y para el desarrollo de futuras terapias para estas afecciones.
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1. Groschwitz KR, Hogan SP. Intestinal barrier function: Molecular regulation and disease pathogenesis. J Allergy Clin Immunol. 2009;124(1):3–20. https://doi.org/10.1016/j.jaci.2009.05.038
2. Coskun M. Intestinal epithelium in inflammatory bowel disease. Front Med. 2014;1(AUG). https://doi.org/ 10.3389/fmed.2014.00024
3. Van Itallie CM, Anderson JM. Claudins and epithelial paracellular transport. Annu Rev Physiol. 2006;68:403–29. https//doi.org/ 10.1146/annurev.physiol.68.040104.131404
4. Suzuki T. Regulation of intestinal epithelial permeability by tight junctions. Cell Mol Life Sci. 2013;70(4):631–59. https//doi.org/ 10.1007/s00018-012-1070-x
5. Mariano C, Sasaki H, Brites D, Brito MA. A look at tricellulin and its role in tight junction formation and maintenance. Eur J Cell Biol. 2011;90(10):787–96. https//doi.org/ 10.1016/j.ejcb.2011.06.002
6. Ebnet K. Junctional adhesion molecules (JAMs): Cell adhesion receptors with pleiotropic functions in cell physiology and development. Physiol Rev. 2017;97(4):1529–54. https//doi.org/ 10.1152/physrev.00004.2017
7. Gumbiner B, Lowenkopf T, Apatira D. Identification of a 160-kDa polypeptide that binds to the tight junction protein ZO-1. Proc Natl Acad Sci U S A. 1991;88(8):3460–4. https//doi.org/ 10.1073/pnas.88.8.3460
8. Willott E, Balda MS, Fanning AS, Jameson B, Van Itallie C, Anderson JM. The tight junction protein ZO-1 is homologous to the Drosophila discs-large tumor suppressor protein of septate junctions. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7834–8. https//doi.org /10.1073/pnas.90.16.783
9. Haskins J, Gu L, Wittchen ES, Hibbard J, Stevenson BR. ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin. J Cell Biol. 1998;141(1):199–208. https//doi.org/ 10.1083/jcb.141.1.199
10. González-Mariscal L, Betanzos A, Nava P, Jaramillo BE. Tight junction proteins. Vol. 81, Progress in Biophysics and Molecular Biology. 2003. p. 1–44. https//doi.org/10.1016/S0079-6107(02)00037-8
11. Fanning AS, Ma TY, Anderson JM. Isolation and functional characterization of the actin binding region in the tight junction protein ZO-1. FASEB J. 2002;16(13):1835–7. https//doi.org/ 10.1096/fj.02-0121fje
12. Chen J, Xiao L, Rao JN, Zou T, Liu L, Bellavance E, et al. JunD represses transcription and translation of the tight junction protein zona occludens-1 modulating intestinal epithelial barrier function. Mol Biol Cell. 2008 Sep;19(9):3701–12. https//doi.org/10.1091/mbc.e08-02-0175
13. Vicario M, Martínez C, Santos J. Role of microRNA in IBS with increased gut permeability. Gut. 2010 Jun;59(6):710–2. https//doi.org/ 10.1136/gut.2009.203695
14. Dietrich CG, Geier A, Oude Elferink RPJ. ABC of oral bioavailability: Transporters as gatekeepers in the gut. Gut. 2003;52(12):1788–95. https//doi.org/
15. Estudante M, Morais JG, Soveral G, Benet LZ. Intestinal drug transporters: An overview. Adv Drug Deliv Rev. 2013;65(10):1340–56. https//doi.org/ 10.1136/gut.52.12.1788
16. Marquez B, Van Bambeke F. ABC Multidrug Transporters: Target for Modulation of Drug Pharmacokinetics and Drug-Drug Interactions. Curr Drug Targets. 2011;12(5):600–20. https//doi.org/ 10.2174/138945011795378504
17. Crawford RR, Potukuchi PK, Schuetz EG, Schuetz JD. Beyond Competitive Inhibition: Regulation of ABC Transporters by Kinases and Protein-Protein Interactions as Potential Mechanisms of Drug-Drug Interactions. Drug Metab Dispos. 2018;46(5):567–80. https//doi.org/ 10.1124/dmd.118.080663
18. Bailey-Dell KJ, Hassel B, Doyle LA, Ross DD. Promoter characterization and genomic organization of the human breast cancer resistance protein (ATP-binding cassette transporter G2) gene. Biochim Biophys Acta - Gene Struct Expr. 2001;1520(3):234–41. https//doi.org/ 10.1016/S0167-4781(01)00270-6
19. Tanaka Y, Slitt AL, Leazer TM, Maher JM, Klaassen CD. Tissue distribution and hormonal regulation of the breast cancer resistance protein (Bcrp/Abcg2) in rats and mice. Biochem Biophys Res Commun. 2004;326(1):181–7. https//doi.org/10.1016/j.bbrc.2004.11.012
20. Natarajan K, Xie Y, Nakanishi T, Beck WT, Bauer KS, Ross DD. Identification and characterization of the major alternative promoter regulating Bcrp1/Abcg2 expression in the mouse intestine. Biochim Biophys Acta - Gene Regul Mech. 2011;1809(7):295–305. https//doi.org/ 10.1016/j.bbagrm.2011.06.004
21. Petrovic V, Teng S, Piquette-miller M. Regulation of drugs transporters during infection and inflammation. Rev Lit Arts Am. 2007;7(2):99–111. https//doi.org/ 10.1124/mi.7.2.10
22. Gutmann H, Hruz P, Zimmermann C, Beglinger C, Drewe J. Distribution of breast cancer resistance protein (BCRP/ABCG2) mRNA expression along the human GI tract. Biochem Pharmacol. 2005;70(5):695–9. https//doi.org/10.1016/j.bcp.2005.05.031
23. Ebert B, Seidel A, Lampen A. Identification of BCRP as transporter of benzo[a]pyrene conjugates metabolically formed in Caco-2 cells and its induction by Ah-receptor agonists. Carcinogenesis. 2005;26(10):1754–63. https//doi.org/ 10.1093/carcin/bgi139
24. Singh A, Wu H, Zhang P, Happel C, Ma J, Biswal S. Expression of ABCG2 (BCRP) Is Regulated by Nrf2 in Cancer Cells That Confers Side Population and Chemoresistance Phenotype. Mol Cancer Ther. 2010 Aug 1;9(8):2365–76. https//doi.org/ 10.1158/1535-7163.MCT-10-0108
25. Ryoo IG, Kim G, Choi BH, Lee SH, Kwak MK. Involvement of NRF2 signaling in doxorubicin resistance of cancer stem cell-enriched colonospheres. Biomol Ther. 2016;24(5):482–8. https//doi.org/ 10.4062/biomolther.2016.145
26. Hirai T, Fukui Y, Motojima K. PPARα agonists positively and negatively regulate the expression of several nutrient/drug transporters in mouse small intestine. Biol Pharm Bull. 2007;30(11):2185–90. https//doi.org/ 10.1248/bpb.30.2185
27. Wright JA, Haslam IS, Coleman T, Simmons NL. Breast cancer resistance protein BCRP (ABCG2)-mediated transepithelial nitrofurantoin secretion and its regulation in human intestinal epithelial (Caco-2) layers. Eur J Pharmacol. 2011;672(1–3):70–6. https//doi.org/ 10.1016/j.ejphar.2011.10.004
28. Natarajan K, Bhullar J, Shukla S, Burcu M, Chen ZS, Ambudkar S V., et al. The Pim kinase inhibitor SGI-1776 decreases cell surface expression of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) and drug transport by Pim-1-dependent and -independent mechanisms. Biochem Pharmacol. 2013;85(4):514–24. https://doi.org/10.1016/j.bcp.2012.12.006
29. Xie Y, Xu K, Linn DE, Yang X, Guo Z, Shimelis H, et al. The 44-kDa Pim-1 kinase phosphorylates BCRP/ABCG2 and thereby promotes its multimerization and drug-resistant activity in human prostate cancer cells. J Biol Chem. 2008;283(6):3349–56. https//doi.org/ 10.1074/jbc.M707773200
30. Draheim V, Reichel A, Weitschies W, Moenning U. N-glycosylation of ABC transporters is associated with functional activity in sandwich-cultured rat hepatocytes. Eur J Pharm Sci. 2010;41(2):201–9.https://doi.org/10.1016/j.ejps.2010.06.005
31. Nakagawa H, Wakabayashi-Nakao K, Tamura A, Toyoda Y, Koshiba S, Ishikawa T. Disruption of N-linked glycosylation enhances ubiquitin-mediated proteasomal degradation of the human ATP-binding cassette transporter ABCG2. FEBS J. 2009 Dec;276(24):7237–52. https//doi.org/ 10.1111/j.1742-4658.2009.07423.x
32. Sugiyama T, Shuto T, Suzuki S, Sato T, Koga T, Suico MA, et al. Posttranslational negative regulation of glycosylated and non-glycosylated BCRP expression by Derlin-1. Biochem Biophys Res Commun. 2011;404:853–8. https://doi.org/10.1016/j.bbrc.2010.12.074
33. Caetano-Pinto P, Jamalpoor A, Ham J, Goumenou A, Mommersteeg M, Pijnenburg D, et al. Cetuximab Prevents Methotrexate-Induced Cytotoxicity in Vitro through Epidermal Growth Factor Dependent Regulation of Renal Drug Transporters. Mol Pharm. 2017 Jun 5;14(6):2147–57. https//doi.org/ 10.1021/acs.molpharmaceut.7b00308
34. Croop J, Housmant D. Mammalian Multidrug Resistance Gene: Complete cDNA Sequence Indicates Strong to Bacterial Transport Proteins. 1986;47. https//doi.org/
35. Gros P, Croop J, Roninson I, Varshavsky A, Housman DE. Isolation and characterization of DNA sequences amplified in multidrug-resistant hamster cells. Proc Natl Acad Sci U S A. 1986;83(2):337–41. https://doi.org/10.1016/0092-8674(86)90594-5
36. Ueda K, Cornwell MM, Gottesman MM, Pastan I, Roninson IB, Ling V, et al. The mdrl gene, responsible for multidrug-resistance, codes for P-glycoprotein. Biochem Biophys Res Commun. 1986;141(3):956–62. https://doi.org/10.1016/S0006-291X(86)80136-X
37. Hsu SIH, Lothstein L, Horwitz SB. Differential overexpression of three mdr gene family members in multidrug-resistant J774.2 mouse cells. Evidence that distinct P-glycoprotein precursors are encoded by unique mdr genes. J Biol Chem. 1989;264(20):12053–62. https//doi.org/ 10.1016/S0021-9258(18)80173-9
38. Mouly S, Paine MF. P-Glycoprotein Increases from Proximal to Distal Regions of Human Small Intestine. Pharm Res. 2003 Oct 1;20(10):1595–9.
39. Jin S, Scotto KW. Transcriptional Regulation of the MDR1 Gene by Histone Acetyltransferase and Deacetylase Is Mediated by NF-Y . Mol Cell Biol. 1998 Jul;18(7):4377–84. https//doi.org/ 10.1128/MCB.18.7.4377
40. Ueda K, Pastan I, Gottesman MM. Isolation and sequence of the promotor region of the human multidrug-resistance (P-glycoprotein) gene. J Biol Chem. 1987;262(36):17432–6. https://doi.org/10.1016/S0021-9258(18)45397-5
41. Cornwell MM, Smith DE. SP1 activates the MDR1 promoter through one of two distinct G-rich regions that modulate promoter activity. J Biol Chem. 1993 Sep 15;268(26):19505–11. https://doi.org/10.1016/S0021-9258(19)36544-5
42. Sundseth R, MacDonald G, Ting J, King AC. DNA elements recognizing NF-Y and Sp1 regulate the human multidrug- resistance gene promoter. Mol Pharmacol. 1997;51(6):963–71. https//doi.org/ 10.1124/mol.51.6.963
43. Gromnicova R, Romero I, Male D. Transcriptional Control of the Multi-Drug Transporter ABCB1 by Transcription Factor Sp3 in Different Human Tissues. PLoS One. 2012 Oct 25;7(10). https//doi.org/ 10.1371/journal.pone.0048189
44. Daschner, P. J., Ciolino, H. P., Plouzek, C. A., Yeh, G. C. Increased AP-1 activity in drug resistant human breast cancer MCF-7 cells. Breast cancer research and treatment, 1999;53,229-240. https//doi.org/ 10.1023/a:1006138803392
45. Chin K-V, Ueda K, Pastan I, Gottesman MM. Modulation of Activity of the Promoter of the Human MDR 1 Gene by Ras and p53. Science (80- ). 1992;255(5043):459–62. https//doi.org/ 10.1126/science.1346476
46. Thottassery J V., Zambettii GP, Arimori K, Schuetz EG, Schuetz JD. p53-dependent regulation of MDR1 gene expression causes selective resistance to chemotherapeutic agents. Proc Natl Acad Sci U S A. 1997;94(20):11037–42. https//doi.org/ 10.1073/pnas.94.20.11037
47. Deng L, Lin-Lee Y-C, Claret F-X, Kuo MT. 2-Acetylaminofluorene Up-regulates Rat mdr1bExpression through Generating Reactive Oxygen Species That Activate NF-κB Pathway *. J Biol Chem. 2001 Jan 5;276(1):413–20. https//doi.org/10.1074/jbc.M004551200
48. Johnson RA, Ince TA, Scotto KW. Transcriptional Repression by p53 through Direct Binding to a Novel DNA Element * 210. J Biol Chem. 2001 Jul 20;276(29):27716–20. https//doi.org/ 10.1074/jbc.C100121200
49. Sampath J, Sun D, Kidd VJ, Grenet J, Gandhi A, Shapiro LH, et al. Mutant p53 Cooperates with ETS and Selectively Up-regulates Human MDR1 Not MRP1 *. J Biol Chem. 2001 Oct 19;276(42):39359–67. https//doi.org/ 10.1074/jbc.M103429200
50. Denison MS, Fisher JM, Whitlock JP. Inducible, receptor-dependent protein-DNA interactions at a dioxin-responsive transcriptional enhancer. Proc Natl Acad Sci U S A. 1988;85(8):2528–32. https//doi.org/ 10.1073/pnas.85.8.252
51. Madden MJ, Morrow CS, Nakagawa M, Goldsmith ME, Fairchild CR, Cowan KH. Identification of 5‘ and 3‘ sequences involved in the regulation of transcription of the human mdr1 gene in vivo. J Biol Chem. 1993 Apr 15;268(11):8290–7. https//doi.org/ https://doi.org/10.1016/S0021-9258(18)53095-7
52. Chan YY, Kalpana S, Chang WC, Chang WC, Chen BK. Expression of aryl hydrocarbon receptor nuclear translocator enhances cisplatin resistance by upregulating MDR1 expression in cancer cells. Mol Pharmacol. 2013;84(4):591–602. https//doi.org/ 10.1124/mol.113.087197
53. Fromm MF, Kauffmann HM, Fritz P, Burk O, Kroemer HK, Warzok RW, et al. The effect of rifampin treatment on intestinal expression of human MRP transporters. Am J Pathol. 2000;157(5):1575–80. https://doi.org/10.1016/S0002-9440(10)64794-3
54. Borst P, Zelcer N, Van De Wetering K, Poolman B. On the putative co-transport of drugs by multidrug resistance proteins. Vol. 580, FEBS Letters. 2006. p. 1085–93. https://doi.org/10.1016/j.febslet.2005.12.039
55. Haimeur A, Conseil G, Deeley RG, Cole SPC. The MRP-related and BCRP/ABCG2 multidrug resistance proteins: Biology, substrate specificity and regulation. Curr Drug Metab. 2004;5(1):21–53.https://doi.org/10.2174/1389200043489199
56. Mottino AD, Hoffman T, Jennes L, Vore M. Expression and Localization of Multidrug Resistant Protein mrp2 in Rat Small Intestine. J Pharmacol Exp Ther. 2000;293(3).
57. Kast HR, Goodwin B, Tarr PT, Jones SA, Anisfeld AM, Stoltz CM, et al. Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J Biol Chem. 2002;277(4):2908–15. https//doi.org/10.1074/jbc.M109326200
58. Chisaki I, Kobayashi M, Itagaki S, Hirano T, Iseki K. Liver X receptor regulates expression of MRP2 but not that of MDR1 and BCRP in the liver. Biochim Biophys Acta - Biomembr. 2009;1788(11):2396–403.https://doi.org/10.1016/j.bbamem.2009.08.014
59. Arana MR, Tocchetti GN, Domizi P, Arias A, Rigalli JP, Ruiz ML, et al. Coordinated induction of GST and MRP2 by cAMP in Caco-2 cells: Role of protein kinase A signaling pathway and toxicological relevance. Toxicol Appl Pharmacol. 2015;287(2):178–90. https://doi.org/10.1016/j.taap.2015.06.003
60. Chai J, Cai SY, Liu X, Lian W, Chen S, Zhang L, et al. Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis. J Hepatol. 2015 Dec 1;63(6):1440–8. https://doi.org/10.1016/j.jhep.2015.07.016
61. Nakano T, Sekine S, Ito K, Horie T. Correlation between apical localization of Abcc2/Mrp2 and phosphorylation status of ezrin in rat intestine. Drug Metab Dispos. 2009 Jul;37(7):1521–7. https//doi.org/ 10.1124/dmd.108.024836
62. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007 Jul;448(7152):427–34. https//doi.org/ 10.1038/nature06005
63. Padoan A, Musso G, Contran N, Basso D. Inflammation, Autoinflammation and Autoimmunity in Inflammatory Bowel Diseases. Vol. 45, Current Issues in Molecular Biology. 2023. p. 5534–57. https//doi.org/ 10.3390/cimb45070350
64. Stürzl M, Kunz M, Krug SM, Naschberger E. Angiocrine Regulation of Epithelial Barrier Integrity in Inflammatory Bowel Disease. Vol. 8, Frontiers in Medicine. Frontiers Media S.A.; 2021. https//doi.org/ 10.3389/fmed.2021.643607
65. Ni J, Wu GD, Albenberg L, Tomov VT. Gut microbiota and IBD: Causation or correlation? Vol. 14, Nature Reviews Gastroenterology and Hepatology. 2017. p. 573–84. https//doi.org/ 10.1038/nrgastro.2017.88
66. Peloquin JM, Goel G, Villablanca EJ, Xavier RJ. Mechanisms of Pediatric Inflammatory Bowel Disease. Vol. 34, Annual Review of Immunology. Annual Reviews Inc.; 2016. p. 31–64. https//doi.org/ 10.1146/annurev-immunol-032414-112151
67. Ng SC, Bernstein CN, Vatn MH, Lakatos PL, Loftusjr E V, Tysk C, et al. Geographical variability and environmental risk factors in inflammatory bowel disease. gut.bmj.comSC Ng, CN Bernstein, MH Vatn, PL Lakatos, EV Loftus, C Tysk, C O’Morain, B MoumGut, 2013•gut.bmj.com. 2013 Apr;62(4):630–49. https://doi.org/10.1136/gutjnl-2012-303661
68. Kaplan GG, Ng SC. Understanding and Preventing the Global Increase of Inflammatory Bowel Disease. Gastroenterology. 2017;152(2):313-321.e2. https://doi.org/10.1053/j.gastro.2016.10.020
69. Sanmarco LM, Chao CC, Wang YC, Kenison JE, Li Z, Rone JM, et al. Identification of environmental factors that promote intestinal inflammation. Nature. 2022 Nov 24;611(7937):801–9. https//doi.org/ 10.1038/s41586-022-05308-6
70. Kaplan GG, Windsor JW. The four epidemiological stages in the global evolution of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2021;18(1):56–66. https//doi.org/ 10.1038/s41575-020-00360-x
71. Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142(1). https://doi.org/10.1053/j.gastro.2011.10.001
72. Sýkora J, Pomahačová R, Kreslová M, Cvalínová D, Štych P, Schwarz J. Current global trends in the incidence of pediatric-onset inflammatory bowel disease. World J Gastroenterol. 2018 Jul 7;24(25):2741–63. https//doi.org/ 10.3748/wjg.v24.i25.2741
73. Burisch J, Munkholm P. The epidemiology of inflammatory bowel disease. Scand J Gastroenterol. 2015 Aug 1;50(8):942–51. https//doi.org/ 10.3109/00365521.2015.1014407
74. Da Silva BC, Lyra AC, Rocha R, Santana GO. Epidemiology, demographic characteristics and prognostic predictors of ulcerative colitis. Vol. 20, World Journal of Gastroenterology. 2014. p. 9458–67. https//doi.org/ 10.3748/wjg.v20.i28.9458
75. Balderramo D, Trakal J, Herrera Najum P, Vivas M, Gonzalez R, Benavidez A, et al. High ulcerative colitis and Crohn’s disease ratio in a population-based registry from Córdoba, Argentina. Dig Liver Dis. 2021;53(7):852–7. https//doi.org/ https://doi.org/10.1016/j.dld.2021.01.006
76. Turpin W, Lee SH, Raygoza Garay JA, Madsen KL, Meddings JB, Bedrani L, et al. Increased Intestinal Permeability Is Associated With Later Development of Crohn’s Disease. Gastroenterology. 2020;159(6):2092-2100.e5. https://doi.org/10.1053/j.gastro.2020.08.005
77. Krug SM, Bojarski C, Fromm A, Lee IM, Dames P, Richter JF, et al. Tricellulin is regulated via interleukin-13-receptor α2, affects macromolecule uptake, and is decreased in ulcerative colitis. Mucosal Immunol. 2018;11(2):345–56. https://doi.org/10.1038/mi.2017.52
78. Oshima T, Miwa H, Joh T. Changes in the expression of claudins in active ulcerative colitis. In: Journal of Gastroenterology and Hepatology (Australia). Blackwell Publishing; 2008. https//doi.org/ 10.1111/j.1440-1746.2008.05405.x
79. Heller F, Florian P, Bojarski C, Richter J, Christ M, Hillenbrand B, et al. Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology. 2005;129(2):550–64. https://doi.org/10.1053/j.gastro.2005.05.002
80. Horowitz A, Chanez-Paredes SD, Haest X, Turner JR. Paracellular permeability and tight junction regulation in gut health and disease. Vol. 20, Nature Reviews Gastroenterology and Hepatology. 2023. p. 417–32. https//doi.org/ 10.1038/s41575-023-00766-3
81. Poritz LS, Garver KI, Green C, Fitzpatrick L, Ruggiero F, Koltun WA. Loss of the Tight Junction Protein ZO-1 in Dextran Sulfate Sodium Induced Colitis. J Surg Res. 2007;140(1):12–9. https://doi.org/10.1016/j.jss.2006.07.050
82. Raju P, Shashikanth N, Tsai PY, Pongkorpsakol P, Chanez-Paredes S, Steinhagen PR, et al. Inactivation of paracellular cation-selective claudin-2 channels attenuates immune-mediated experimental colitis in mice. J Clin Invest. 2020;130(10):5197–208. https//doi.org/ 10.1172/JCI138697
83. Dommels YEM, Butts CA, Zhu S, Davy M, Martell S, Hedderley D, et al. Characterization of intestinal inflammation and identification of related gene expression changes in mdr1a-/- mice. Genes Nutr. 2007 Nov;2(2):209–23. https//doi.org/ 10.1007/s12263-007-0051-4
84. Collett A, Higgs NB, Gironella M, Zeef LAH, Hayes A, Salmo E, et al. Early molecular and functional changes in colonic epithelium that precede increased gut permeability during colitis development in mdr1a(−/−) mice. Inflamm Bowel Dis. 2008 May;14(5):620–31. https//doi.org/ 10.1002/ibd.20375
85. Nones K, Knoch B, Dommels YEM, Paturi G, Butts C, Mcnabb WC, et al. Multidrug resistance gene deficient (mdr1a–/–) mice have an altered caecal microbiota that precedes the onset of intestinal inflammation. Journal Appl Microbiol. 2009;107(2):557–66. https//doi.org/ 10.1111/j.1365-2672.2009.04225.x
86. Young VB, Chien CC, Knox KA, Taylor NS, Schauer DB, Fox JG. Cytolethal distending toxin in avian and human isolates of Helicobacter pullorum. J Infect Dis. 2000;182(2):620–3. https//doi.org/ 10.1086/315705
87. Frank DN, St. Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13780–5. https//doi.org/ 10.1073/pnas.070662510
88. Huang B, Chen Z, Geng L, Wang J, Liang H, Cao Y, et al. Mucosal Profiling of Pediatric-Onset Colitis and IBD Reveals Common Pathogenics and Therapeutic Pathways. Cell. 2019 Nov;179(5):1160-1176.e24. https://doi.org/10.1016/j.cell.2019.10.027
89. Englund G, Jacobson A, Rorsman F, Artursson P, Kindmark A, Rönnblom A. Efflux transporters in ulcerative colitis: Decreased expression of BCRP (ABCG2) and Pgp (ABCB1). Inflamm Bowel Dis. 2007;13(3):291–7. https//doi.org/ 10.1002/ibd.20030
90. Jahnel J, Fickert P, Hauer AC, Högenauer C, Avian A, Trauner M. Inflammatory bowel disease alters intestinal bile acid transporter expression. ASPETJ Jahnel, P Fickert, AC Hauer, C Högenauer, A Avian, M TraunerDrug Metab Dispos 2014•ASPET. 2014;42:1423–31. https//doi.org/ 10.1124/dmd.114.058065
91. Erdmann P, Bruckmueller H, Martin P, Busch D, Haenisch S, Müller J, et al. Dysregulation of Mucosal Membrane Transporters and Drug-Metabolizing Enzymes in Ulcerative Colitis. J Pharm Sci. 2019;108(2):1035–46. https://doi.org/10.1016/j.xphs.2018.09.024
92. Langmann T, Moehle C, Mauerer R, Scharl M, Liebisch G, Zahn A, et al. Loss of detoxification in inflammatory bowel disease: Dysregulation of pregnane X receptor target genes. Gastroenterology. 2004;127(1):26–40. https://doi.org/10.1053/j.gastro.2004.04.019
93. Pazos M, Siccardi D, Mumy KL, Bien JD, Louie S, Shi HN, et al. Multidrug Resistance-Associated Transporter 2 Regulates Mucosal Inflammation by Facilitating the Synthesis of Hepoxilin A3. J Immunol. 2008;181(11):8044–52. https://doi.org/10.4049/jimmunol.181.11.8044
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