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Нарушение проницаемости слизистой оболочки как фактор патогенеза функциональных нарушений желудочно-кишечного тракта: обоснование и возможности коррекции
Нарушение проницаемости слизистой оболочки как фактор патогенеза функциональных нарушений желудочно-кишечного тракта: обоснование и возможности коррекции
Вялов С.С. Нарушение проницаемости слизистой оболочки как фактор патогенеза функциональных нарушений желудочно-кишечного тракта: обоснование и возможности коррекции. Consilium Medicum. 2018; 20 (12): 99–104. DOI: 10.26442/20751753.2018.12.180062
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Аннотация
В статье приводится обзор современных представлений о строении слизисто-эпителиального барьера и его проницаемости. Обсуждается взаимосвязь нарушений функции желудочно-кишечного тракта и нарушения структуры плотных контактов. Анализируются диагностические возможности исследования проницаемости и барьерной функции эпителия в реальной практике и клинических исследованиях. Описан вклад нарушений проницаемости в патогенез различных функциональных заболеваний желудочно-кишечного тракта.
Ключевые слова: проницаемость, эпителий, барьерная функция, плотные контакты, ребамипид.
Ключевые слова: проницаемость, эпителий, барьерная функция, плотные контакты, ребамипид.
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The article presents modern view on mucosal epithelial barrier structure and its permeability. Interrelation of gastrointestinal tract dysfunction and tight junctions’ structural damage is discussed. Diagnostic possibilities of epithelium permeability and barrier function study in everyday practice and clinical studies are analyzed. Contribution of permeability disturbances in pathogenesis of different gastrointestinal tract functional disorders is discussed.
Key words: permeability, epithelium, barrier function, tight junctions, rebamipide.
Key words: permeability, epithelium, barrier function, tight junctions, rebamipide.
Полный текст
Список литературы
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2. Spadoni I, Zagato E, Bertocchi A et al. A gut-vascular barrier controls the systemic dissemination of bacteria. Science 2015; 350 (6262): 830–4. DOI: 10.1126/science.aad0135
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4. Johansson ME, Phillipson M, Petersson J et al. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci U S A. 2008; 105 (39): 15064–9. DOI: 10.1073/pnas.0803124105
5. Van der Sluis M, De Koning BA, De Bruijn AC et al. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 2006; 131 (1): 117–29.
6. Johansson ME. Mucus layers in inflammatory bowel disease. Inflamm Bowel Dis 2014; 20 (11): 2124–31. DOI: 10.1097/MIB.0000000000000117
7. Shen L, Weber CR, Raleigh DR et al. Tight junction pore and leak pathways: a dynamic duo. Annu Rev Physiol 2011; 73: 283–309. DOI: 10.1146/annurev-physiol-012110-142150
8. Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2001; 2 (4): 285–93.
9. Suzuki H, Tani K, Tamura A et al. Model for the architecture of claudin-based paracellular ion channels through tight junctions. J Mol Biol 2015; 427 (2): 291–7. DOI: 10.1016/j.jmb.2014.10.020
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11. Van Itallie CM, Holmes J, Bridges A et al. The density of small tight junction pores varies among cell types and is increased by expression of claudin-2. J Cell Sci 2008; 121 (Pt 3): 298–305. DOI: 10.1242/jcs.021485
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13. Heller F, Florian P, Bojarski C 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.
14. Turner JR, Rill BK, Carlson SL et al. Physiological regulation of epithelial tight junctions is associated with myosin light-chain phosphorylation. Am J Physiol 1997; 273 (4 Pt 1): C1378–85.
15. Clayburgh DR, Musch MW, Leitges M et al. Coordinated epithelial NHE3 inhibition and barrier dysfunction are required for TNF-mediated diarrhea in vivo. J Clin Invest 2006; 116 (10): 2682–94.
16. Su L, Nalle SC, Shen et al. TNFR2 activates MLCK-dependent tight junction dysregulation to cause apoptosis-mediated barrier loss and experimental colitis. Gastroenterology 2013; 145 (2): 407–15. DOI: 10.1053/j.gastro.2013.04.011
17. Odenwald MA, Turner JR. The intestinal epithelial barrier: a therapeutic target? Nat Rev Gastroenterol Hepatol 2017; 14 (1): 9–21. DOI: 10.1038/nrgastro.2016.169
18. Farré R, Vicario M. Abnormal Barrier Function in Gastrointestinal Disorders. Handb Exp Pharmacol 2017; 239: 193–217. DOI: 10.1007/164_2016_107
19. Bednarska O, Walter SA, Casado-Bedmar M et al. Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syndrome. Gastroenterology 2017; 153 (4): 948–60.e3. DOI: 10.1053/j.gastro.2017.06.051
20. Vanuytsel T, van Wanrooy S, Vanheel H et al. Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut 2014; 63 (8): 1293–9. DOI: 10.1136/gutjnl-2013-305690
21. France MM, Turner JR. The mucosal barrier at a glance. J Cell Sci 2017; 130 (2): 307–14. DOI: 10.1242/jcs.193482
22. Barbaro MR, Fuschi D, Cremon C et al. Escherichia coli Nissle 1917 restores epithelial permeability alterations induced by irritable bowel syndrome mediators. Neurogastroenterol Motil 2018; e13388. DOI: 10.1111/nmo.13388
23. Bischoff SC, Barbara G, Buurman W et al. Intestinal permeability – a new target for disease prevention and therapy. BMC Gastroenterol 2014; 14: 189. DOI: 10.1186/s12876-014-0189-7
24. Statovci D, Aguilera M, MacSharry J, Melgar S. The Impact of Western Diet and Nutrients on the Microbiota and Immune Response at Mucosal Interfaces. Front Immunol 2017; 8: 838. DOI: 10.3389/fimmu.2017.00838
25. Buhner S, Buning C, Genschel J et al. Genetic basis for increased intestinal permeability in families with Crohn's disease: role of CARD15 3020insC mutation? Gut 2006; 55 (3): 342–7.
26. Aguas M, Garrigues V, Bastida G et al. Prevalence of irritable bowel syndrome (IBS) in first-degree relatives of patients with inflammatory bowel disease (IBD). J Crohns Colitis 2011; 5 (3): 227–33. DOI: 10.1016/j.crohns.2011.01.008
27. Barbara G, Feinle-Bisset C, Ghoshal UC et al. The Intestinal Microenvironment and Functional Gastrointestinal Disorders. Gastroenterology 2016. pii: S0016-5085(16)00219-5. DOI: 10.1053/j.gastro.2016.02.028
28. D'Incà R, Di Leo V, Corrao G et al. Intestinal permeability test as a predictor of clinical course in Crohn's disease. Am J Gastroenterol 1999; 94 (10): 2956–60.
29. Odenwald MA, Turner JR. Intestinal permeability defects: is it time to treat? Clin Gastroenterol Hepatol 2013; 11 (9): 1075–83. DOI: 10.1016/j.cgh.2013.07.001
30. Spiller RC, Jenkins D, Thornley JP et al. Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut 2000; 47 (6): 804–11.
31. Zhou Q, Zhang B, Verne GN. Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome. Pain 2009; 146 (1–2): 41–6. DOI: 10.1016/j.pain.2009.06.017
32. Martínez C, Lobo B, Pigrau M et al. Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier. Gut 2013; 62 (8): 1160–8. DOI: 10.1136/gutjnl-2012-302093
33. Piche T, Barbara G, Aubert P et al. Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators. Gut 2009; 58 (2): 196–201. DOI: 10.1136/gut.2007.140806
34. Vanheel H, Vicario M, Vanuytsel T et al. Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia. Gut 2014; 63 (2): 262–71. DOI: 10.1136/gutjnl-2012-303857
35. Vivinus-Nébot M, Dainese R, Anty R et al. Combination of allergic factors can worsen diarrheic irritable bowel syndrome: role of barrier defects and mast cells. Am J Gastroenterol 2012; 107 (1): 75–81. DOI: 10.1038/ajg.2011.315
36. Fritscher-Ravens A, Schuppan D, Ellrichmann M et al. Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology 2014; 147 (5): 1012–20.e4. DOI: 10.1053/j.gastro.2014.07.046
37. Sapone A, Bai JC, Ciacci C et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med 2012; 10: 13. DOI: 10.1186/1741-7015-10-13
38. Lijima K et al. Rebamipide, a Cytoprotective Drug, Increases Gastric Mucus Secretion in Human: Evaluations with Endoscopic Gastrin Test. Dig Dis Sci 2009; 54 (7): 1500–7.
39. Haruma K, Ito M. Review article: clinical significance of mucosal-protective agents: acid, inflammation, carcinogenesis and rebamipide. Aliment Pharmacol Ther 2003; 18 (Suppl. 1): 153–9.
40. Tarnawski AS, Chai J, Pai R, Chiou SK. Rebamipide activates genes encoding angiogenic growth factors and Cox2 and stimulates angiogenesis: a key to its ulcer healing action? Dig Dis Sci 2004; 49 (2): 202–9.
41. Ishihara K et al. Effect of rebamipide on mucus secretion by endogenous prostaglandin-independent mechanism in rat gastric mucosa. Arzneimittelforschung 1992; 42 (12): 1462–6.
42. Suzuki T et al. Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution. J Pharmacol Sci 2008; 106: 469–77.
43. Nagano Y et al. Rebamipide significantly inhibits indomethacin-induced mitochondrial damage, lipid peroxidation, and apoptosis in gastric epithelial RGM-1 cells. Dig Dis Sci 2005; 50 (Suppl. 1): 76–83.
44. Lai Yu et al. Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of b-Catenin. PLoS ONE 2015; 10.
45. Jaafar MH, Safi SZ, Tan MP et al. Efficacy of Rebamipide in Organic and Functional Dyspepsia: A Systematic Review and Meta-Analysis. Dig Dis Sci 2018; 63 (5): 1250–60. DOI: 10.1007/s10620-017-4871-9
46. Vyalov S. Efficacy of rebamipide to prevent low-dose aspirin-induced small intestinal injury. UEG Journal 2017; 5 (5S): a827, P1938.
47. Vyalov S. Efficacy and tolerability of rebamipide in triple therapy for eradication of Helicobacter pylori: a randomized clinical trial. UEG Journal 2017; 5 (5S): a605, P1261.
48. Vialov S.S. Vosstanovlenie slizistoi obolochki zheludochno-kishechnogo trakta ili snizhenie kislotnosti zheludka. Prioritety v lechenii. Effektivnaia farmakoterapiia. 2016; 1. [in Russian]
49. Du Y, Li Z, Zhan X et al. Anti-inflammatory effects of rebamipide according to Helicobacter pylori status in patients with chronic erosive gastritis: a randomized sucralfate-controlled multicenter trial in China-STARS study. Dig Dis Sci 2008; 53 (11): 2886–95. DOI: 10.1007/s10620-007-0180-z
2. Spadoni I, Zagato E, Bertocchi A et al. A gut-vascular barrier controls the systemic dissemination of bacteria. Science 2015; 350 (6262): 830–4. DOI: 10.1126/science.aad0135
3. Johansson ME, Sjövall H, Hansson GC. The gastrointestinal mucus system in health and disease. Nat Rev Gastroenterol Hepatol 2013; 10 (6): 352–61. DOI: 10.1038/nrgastro.2013.35
4. Johansson ME, Phillipson M, Petersson J et al. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci U S A. 2008; 105 (39): 15064–9. DOI: 10.1073/pnas.0803124105
3. Johansson ME, Sjövall H, Hansson GC. The gastrointestinal mucus system in health and disease. Nat Rev Gastroenterol Hepatol 2013; 10 (6): 352–61. DOI: 10.1038/nrgastro.2013.35
4. Johansson ME, Phillipson M, Petersson J et al. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci U S A. 2008; 105 (39): 15064–9. DOI: 10.1073/pnas.0803124105
5. Van der Sluis M, De Koning BA, De Bruijn AC et al. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 2006; 131 (1): 117–29.
6. Johansson ME. Mucus layers in inflammatory bowel disease. Inflamm Bowel Dis 2014; 20 (11): 2124–31. DOI: 10.1097/MIB.0000000000000117
7. Shen L, Weber CR, Raleigh DR et al. Tight junction pore and leak pathways: a dynamic duo. Annu Rev Physiol 2011; 73: 283–309. DOI: 10.1146/annurev-physiol-012110-142150
8. Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2001; 2 (4): 285–93.
9. Suzuki H, Tani K, Tamura A et al. Model for the architecture of claudin-based paracellular ion channels through tight junctions. J Mol Biol 2015; 427 (2): 291–7. DOI: 10.1016/j.jmb.2014.10.020
10. Anderson JM, Van Itallie CM. Tight junctions. Curr Biol 2008; 18 (20): R941–3. DOI: 10.1016/j.cub.2008.07.083
10. Anderson JM, Van Itallie CM. Tight junctions. Curr Biol 2008; 18 (20): R941–3. DOI: 10.1016/j.cub.2008.07.083
11. Van Itallie CM, Holmes J, Bridges A et al. The density of small tight junction pores varies among cell types and is increased by expression of claudin-2. J Cell Sci 2008; 121 (Pt 3): 298–305. DOI: 10.1242/jcs.021485
12. Weber CR, Raleigh DR, Su L et al. Epithelial myosin light chain kinase activation induces mucosal interleukin-13 expression to alter tight junction ion selectivity. J Biol Chem 2010; 285 (16): 12037–46. DOI: 10.1074/jbc.M109.064808
13. Heller F, Florian P, Bojarski C 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.
14. Turner JR, Rill BK, Carlson SL et al. Physiological regulation of epithelial tight junctions is associated with myosin light-chain phosphorylation. Am J Physiol 1997; 273 (4 Pt 1): C1378–85.
15. Clayburgh DR, Musch MW, Leitges M et al. Coordinated epithelial NHE3 inhibition and barrier dysfunction are required for TNF-mediated diarrhea in vivo. J Clin Invest 2006; 116 (10): 2682–94.
16. Su L, Nalle SC, Shen et al. TNFR2 activates MLCK-dependent tight junction dysregulation to cause apoptosis-mediated barrier loss and experimental colitis. Gastroenterology 2013; 145 (2): 407–15. DOI: 10.1053/j.gastro.2013.04.011
17. Odenwald MA, Turner JR. The intestinal epithelial barrier: a therapeutic target? Nat Rev Gastroenterol Hepatol 2017; 14 (1): 9–21. DOI: 10.1038/nrgastro.2016.169
18. Farré R, Vicario M. Abnormal Barrier Function in Gastrointestinal Disorders. Handb Exp Pharmacol 2017; 239: 193–217. DOI: 10.1007/164_2016_107
19. Bednarska O, Walter SA, Casado-Bedmar M et al. Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syndrome. Gastroenterology 2017; 153 (4): 948–60.e3. DOI: 10.1053/j.gastro.2017.06.051
20. Vanuytsel T, van Wanrooy S, Vanheel H et al. Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut 2014; 63 (8): 1293–9. DOI: 10.1136/gutjnl-2013-305690
21. France MM, Turner JR. The mucosal barrier at a glance. J Cell Sci 2017; 130 (2): 307–14. DOI: 10.1242/jcs.193482
22. Barbaro MR, Fuschi D, Cremon C et al. Escherichia coli Nissle 1917 restores epithelial permeability alterations induced by irritable bowel syndrome mediators. Neurogastroenterol Motil 2018; e13388. DOI: 10.1111/nmo.13388
23. Bischoff SC, Barbara G, Buurman W et al. Intestinal permeability – a new target for disease prevention and therapy. BMC Gastroenterol 2014; 14: 189. DOI: 10.1186/s12876-014-0189-7
24. Statovci D, Aguilera M, MacSharry J, Melgar S. The Impact of Western Diet and Nutrients on the Microbiota and Immune Response at Mucosal Interfaces. Front Immunol 2017; 8: 838. DOI: 10.3389/fimmu.2017.00838
25. Buhner S, Buning C, Genschel J et al. Genetic basis for increased intestinal permeability in families with Crohn's disease: role of CARD15 3020insC mutation? Gut 2006; 55 (3): 342–7.
26. Aguas M, Garrigues V, Bastida G et al. Prevalence of irritable bowel syndrome (IBS) in first-degree relatives of patients with inflammatory bowel disease (IBD). J Crohns Colitis 2011; 5 (3): 227–33. DOI: 10.1016/j.crohns.2011.01.008
27. Barbara G, Feinle-Bisset C, Ghoshal UC et al. The Intestinal Microenvironment and Functional Gastrointestinal Disorders. Gastroenterology 2016. pii: S0016-5085(16)00219-5. DOI: 10.1053/j.gastro.2016.02.028
28. D'Incà R, Di Leo V, Corrao G et al. Intestinal permeability test as a predictor of clinical course in Crohn's disease. Am J Gastroenterol 1999; 94 (10): 2956–60.
29. Odenwald MA, Turner JR. Intestinal permeability defects: is it time to treat? Clin Gastroenterol Hepatol 2013; 11 (9): 1075–83. DOI: 10.1016/j.cgh.2013.07.001
30. Spiller RC, Jenkins D, Thornley JP et al. Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut 2000; 47 (6): 804–11.
31. Zhou Q, Zhang B, Verne GN. Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome. Pain 2009; 146 (1–2): 41–6. DOI: 10.1016/j.pain.2009.06.017
32. Martínez C, Lobo B, Pigrau M et al. Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier. Gut 2013; 62 (8): 1160–8. DOI: 10.1136/gutjnl-2012-302093
33. Piche T, Barbara G, Aubert P et al. Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators. Gut 2009; 58 (2): 196–201. DOI: 10.1136/gut.2007.140806
34. Vanheel H, Vicario M, Vanuytsel T et al. Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia. Gut 2014; 63 (2): 262–71. DOI: 10.1136/gutjnl-2012-303857
35. Vivinus-Nébot M, Dainese R, Anty R et al. Combination of allergic factors can worsen diarrheic irritable bowel syndrome: role of barrier defects and mast cells. Am J Gastroenterol 2012; 107 (1): 75–81. DOI: 10.1038/ajg.2011.315
36. Fritscher-Ravens A, Schuppan D, Ellrichmann M et al. Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology 2014; 147 (5): 1012–20.e4. DOI: 10.1053/j.gastro.2014.07.046
37. Sapone A, Bai JC, Ciacci C et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med 2012; 10: 13. DOI: 10.1186/1741-7015-10-13
38. Lijima K et al. Rebamipide, a Cytoprotective Drug, Increases Gastric Mucus Secretion in Human: Evaluations with Endoscopic Gastrin Test. Dig Dis Sci 2009; 54 (7): 1500–7.
39. Haruma K, Ito M. Review article: clinical significance of mucosal-protective agents: acid, inflammation, carcinogenesis and rebamipide. Aliment Pharmacol Ther 2003; 18 (Suppl. 1): 153–9.
40. Tarnawski AS, Chai J, Pai R, Chiou SK. Rebamipide activates genes encoding angiogenic growth factors and Cox2 and stimulates angiogenesis: a key to its ulcer healing action? Dig Dis Sci 2004; 49 (2): 202–9.
41. Ishihara K et al. Effect of rebamipide on mucus secretion by endogenous prostaglandin-independent mechanism in rat gastric mucosa. Arzneimittelforschung 1992; 42 (12): 1462–6.
42. Suzuki T et al. Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution. J Pharmacol Sci 2008; 106: 469–77.
43. Nagano Y et al. Rebamipide significantly inhibits indomethacin-induced mitochondrial damage, lipid peroxidation, and apoptosis in gastric epithelial RGM-1 cells. Dig Dis Sci 2005; 50 (Suppl. 1): 76–83.
44. Lai Yu et al. Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of b-Catenin. PLoS ONE 2015; 10.
45. Jaafar MH, Safi SZ, Tan MP et al. Efficacy of Rebamipide in Organic and Functional Dyspepsia: A Systematic Review and Meta-Analysis. Dig Dis Sci 2018; 63 (5): 1250–60. DOI: 10.1007/s10620-017-4871-9
46. Vyalov S. Efficacy of rebamipide to prevent low-dose aspirin-induced small intestinal injury. UEG Journal 2017; 5 (5S): a827, P1938.
47. Vyalov S. Efficacy and tolerability of rebamipide in triple therapy for eradication of Helicobacter pylori: a randomized clinical trial. UEG Journal 2017; 5 (5S): a605, P1261.
48. Вялов С.С. Восстановление слизистой оболочки желудочно-кишечного тракта или снижение кислотности желудка. Приоритеты в лечении. Эффективная фармакотерапия. 2016; 1. / Vialov S.S. Vosstanovlenie slizistoi obolochki zheludochno-kishechnogo trakta ili snizhenie kislotnosti zheludka. Prioritety v lechenii. Effektivnaia farmakoterapiia. 2016; 1. [in Russian]
49. Du Y, Li Z, Zhan X et al. Anti-inflammatory effects of rebamipide according to Helicobacter pylori status in patients with chronic erosive gastritis: a randomized sucralfate-controlled multicenter trial in China-STARS study. Dig Dis Sci 2008; 53 (11): 2886–95. DOI: 10.1007/s10620-007-0180-z
________________________________________________
2. Spadoni I, Zagato E, Bertocchi A et al. A gut-vascular barrier controls the systemic dissemination of bacteria. Science 2015; 350 (6262): 830–4. DOI: 10.1126/science.aad0135
3. Johansson ME, Sjövall H, Hansson GC. The gastrointestinal mucus system in health and disease. Nat Rev Gastroenterol Hepatol 2013; 10 (6): 352–61. DOI: 10.1038/nrgastro.2013.35
4. Johansson ME, Phillipson M, Petersson J et al. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci U S A. 2008; 105 (39): 15064–9. DOI: 10.1073/pnas.0803124105
5. Van der Sluis M, De Koning BA, De Bruijn AC et al. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 2006; 131 (1): 117–29.
6. Johansson ME. Mucus layers in inflammatory bowel disease. Inflamm Bowel Dis 2014; 20 (11): 2124–31. DOI: 10.1097/MIB.0000000000000117
7. Shen L, Weber CR, Raleigh DR et al. Tight junction pore and leak pathways: a dynamic duo. Annu Rev Physiol 2011; 73: 283–309. DOI: 10.1146/annurev-physiol-012110-142150
8. Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2001; 2 (4): 285–93.
9. Suzuki H, Tani K, Tamura A et al. Model for the architecture of claudin-based paracellular ion channels through tight junctions. J Mol Biol 2015; 427 (2): 291–7. DOI: 10.1016/j.jmb.2014.10.020
10. Anderson JM, Van Itallie CM. Tight junctions. Curr Biol 2008; 18 (20): R941–3. DOI: 10.1016/j.cub.2008.07.083
11. Van Itallie CM, Holmes J, Bridges A et al. The density of small tight junction pores varies among cell types and is increased by expression of claudin-2. J Cell Sci 2008; 121 (Pt 3): 298–305. DOI: 10.1242/jcs.021485
12. Weber CR, Raleigh DR, Su L et al. Epithelial myosin light chain kinase activation induces mucosal interleukin-13 expression to alter tight junction ion selectivity. J Biol Chem 2010; 285 (16): 12037–46. DOI: 10.1074/jbc.M109.064808
13. Heller F, Florian P, Bojarski C 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.
14. Turner JR, Rill BK, Carlson SL et al. Physiological regulation of epithelial tight junctions is associated with myosin light-chain phosphorylation. Am J Physiol 1997; 273 (4 Pt 1): C1378–85.
15. Clayburgh DR, Musch MW, Leitges M et al. Coordinated epithelial NHE3 inhibition and barrier dysfunction are required for TNF-mediated diarrhea in vivo. J Clin Invest 2006; 116 (10): 2682–94.
16. Su L, Nalle SC, Shen et al. TNFR2 activates MLCK-dependent tight junction dysregulation to cause apoptosis-mediated barrier loss and experimental colitis. Gastroenterology 2013; 145 (2): 407–15. DOI: 10.1053/j.gastro.2013.04.011
17. Odenwald MA, Turner JR. The intestinal epithelial barrier: a therapeutic target? Nat Rev Gastroenterol Hepatol 2017; 14 (1): 9–21. DOI: 10.1038/nrgastro.2016.169
18. Farré R, Vicario M. Abnormal Barrier Function in Gastrointestinal Disorders. Handb Exp Pharmacol 2017; 239: 193–217. DOI: 10.1007/164_2016_107
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Авторы
С.С.Вялов
Клиника GMS. 121099, Россия, Москва, 1-й Николощеповский пер., д. 6, стр. 1
svialov@mail.ru
Клиника GMS. 121099, Россия, Москва, 1-й Николощеповский пер., д. 6, стр. 1
svialov@mail.ru
________________________________________________
S.S.Vialov
GMS Clinic. 121099, Russian Federation, Moscow, 1-i Nikoloshchepovskii per., d. 6, str. 1
svialov@mail.ru
GMS Clinic. 121099, Russian Federation, Moscow, 1-i Nikoloshchepovskii per., d. 6, str. 1
svialov@mail.ru
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