1. Федеральное государственное бюджетное научное учреждение «Научно-исследовательский институт морфологии человека», 117418, г. Москва, Россия
2. Федеральное государственное бюджетное образовательное учреждение высшего образования «Ингушский государственный университет», 386001, г. Магас, Россия
3. Федеральное Государственное Бюджетное Образовательное Учреждение Высшего Образования «Московский государственный медикостоматологический университет имени А. И. Евдокимова» Министерства здравоохранения Российской Федерации, 127473, г. Москва, Россия

Ключевые слова: толстая кишка, эпителиальный барьер, слизь, гликокаликс, муц ины, плотные контакты, иммунная система, язвенный колит

Резюме:В толстой кишке присутствует огромное количество комменсальных бактерий и пищевых антигенов, в тоже время в кишечник могут попадать и патогенные микроорганизмы. Макроорганизму необходимо сохранять толерантность к первым и развивать эффективный иммунный ответ на последние. Ведущую роль в реализации этой задачи играет эпителиальный барьер толстой кишки. Нарушение функции эпителиального барьера приводит к развитию воспалительного ответа на нормальные кишечные антигены, что, по мнению ряда авторов, является инициальным механизмом развития язвенного колита. Данный обзор посвящен современным представлениям о строении и функции эпителиального барьера толстой кишки и его нарушениям при язвенном колите.

• Литература всего 64 ⇓ :: .
  1. Merga Y., Campbell B. J., Rhodes J. M. Mucosal barrier, bacteria and infl ammatory bowel disease: possibilities for therapy. Dig Dis. 2014;32(4):475–83. doi: 10.1159/000358156.
  2. Roda G., Sartini A, Zambon E, Calafi ore A, Marocchi M, Caponi A, Belluzzi A, Roda E. Intestinal epithelial cells in infl ammatory bowel diseases. World J Gastroenterol. 2010; 16(34):4264–71.
  3. Zolotova N. A., Makarova O. V. Barrier function of colonic mucins in health and ulcerative colitis. Clinical and experimental morphology. 2016; 3(19): 69–74.
  4. Geremia A., Biancheri P, Allan P, Corazza GR, Di Sabatino A. Innate and adaptive immunity in infl ammatory bowel disease. Autoimmun Rev. 2014; 13(1):3–10. doi: 10.1016/j.autrev.2013.06.004.
  5. Tkachev A. V., Mkrtchyan L. S., Nikitina K. E. Features of epidemiology and etiopathogenesis of infl ammatory bowel disease: state of the problem. Nauchnaya mysl’ Kavkaza. 2001; 2: 175–180.
  6. Coskun M. Intestinal epithelium in infl ammatory bowel disease. Front Med (Lausanne). 2014; 1:24. doi: 10.3389/ fmed.2014.00024.
  7. Deplancke B., Gaskins H. R. Microbial modulation of innate defense: goblet cells and the intestinal mucus layer. Am J Clin Nutr. 2001; 73(6):1131S-1141S.
  8. Mogilnaja G. M., Mogilnaja V. L. A gastrointestinal protective barrier. Morphologiya. 2007; 132(6): 9–16
  9. Jonckheere N., Skrypek N., Frénois F., Van Seuningen I. Membrane-bound mucin modular domains: from structure to function. Biochimie. 2013; 95(6):1077–86. doi: 10.1016/j.biochi.2012.11.005.
  10. Corfi eld A. P., Carroll D., Myerscough N., Probert C. S. Mucins in the gastrointestinal tract in health and disease. Front Biosci. 2001; 6: D1321–57.
  11. Pelaseyed T., Bergström J. H., Gustafsson J. K., Ermund A., Birchenough G. M., Schütte A., van der Post S., Svensson F., Rodríguez-Piñeiro A. M., Nyström E. E., Wising C., Johansson M. E., Hansson G. C. Th e mucus and mucins of the goblet cells and enterocytes provide the fi rst defense line of the gastrointestinal tract and interact with the immune system. Immunol Rev. 2014; 260(1):8–20. doi: 10.1111/imr.12182.
  12. Tobisawa Y., Imai Y., Fukuda M., Kawashima H. Sulfation of colonic mucins by N-acetylglucosamine 6-O-sulfotransferase-2 and its protective function in experimental colitis in mice. J Biol Chem. 2010; 285(9):6750–60. doi: 10.1074/jbc.M109.067082.
  13. Kim Y. S., Ho S. B. Intestinal goblet cells and mucins in health and disease: recent insights and progress. Curr Gastroenterol Rep. 2010; 12(5):319–30. doi: 10.1007/ s11894–010–0131–2.
  14. Corfi eld A. P., Wagner S. A, O’Donnell L. J, Durdey P., Mountford R. A., Clamp J. R. Th e roles of enteric bacterial sialidase, sialate O-acetyl esterase and glycosulfatase in the degradation of human colonic mucin. Glycoconj J. 1993; 10(1):72–81
  15. Johansson M. E., Gustafsson J. K., Sjöberg K. E., Petersson J., Holm L., Sjövall H., Hansson G. C. Bacteria penetrate the inner mucus layer before infl ammation in the dextran sulfate colitis model. PLoS One. 2010; 5(8): e12238. doi: 10.1371/journal.pone.0012238
  16. Pullan R. D., Th omas G. A., Rhodes M., Newcombe R. G., Williams G. T., Allen A., Rhodes J. Th ickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis. Gut. 1994; 35(3):353–9.
  17. Dorofeev A. E., Vasilenko I. V., Rassokhina O. A. Izmeneniya ehkspressii MUC2, MUC3, MUC4, TFF3 v slizistoj obolochke tolstogo kishechnika u bol’nykh nespetsifi cheskim yazvennym kolitom [Changes in the expression of MUC2, MUC3, MUC4, TFF3 in the mucous membrane of the large intestine in patients with ulcerative colitis]. Gastroenterologіya – [Gastroenterologiya], 2013; 1(47): 80–84.
  18. Bustos D., Negri G, De Paula JA, Di Carlo M, Yapur V, Facente A, De Paula A. Colonic proteinases: increased activity in patients with ulcerative colitis. Medicina (B Aires). 1998;58(3):262–4.
  19. Tsai H. H., Dwarakanath AD, Hart CA, Milton JD, Rhodes JM. Increased faecal mucin sulphatase activity in ulcerative colitis: a potential target for treatment. Gut. 1995 Apr;36(4):570–6.
  20. Moehle C., Ackermann N, Langmann T, Aslanidis C, Kel A, Kel-Margoulis O, Schmitz-Madry A, Zahn A, Stremmel W, Schmitz G. Aberrant intestinal expression and allelic variants of mucin genes associated with infl ammatory bowel disease. J Mol Med (Berl). 2006; 84(12):1055–66
  21. Senapati S., Ho SB, Sharma P, Das S, Chakraborty S, Kaur S, Niehans G, Batra SK. Expression of intestinal MUC17 membrane-bound mucin in infl ammatory and neoplastic diseases of the colon. J Clin Pathol. 2010; 63(8):702–7. doi: 10.1136/jcp.2010.078717.
  22. Van Klinken B. J., Van der Wal JW, Einerhand AW, Büller HA, Dekker J. Sulphation and secretion of the predominant secretory human colonic mucin MUC2 in ulcerative colitis. Gut. 1999; 44(3):387–93.
  23. Tytgat K. M., van der Wal JW, Einerhand AW, Büller HA, Dekker J. Quantitative analysis of MUC2 synthesis in ulcerative colitis. Biochem Biophys Res Commun. 1996; 224(2):397–405.
  24. Hanski C., Born M, Foss HD, Marowski B, Mansmann U, Arastéh K, Bachler B, Papenfuss M, Niedobitek F. Defective post-transcriptional processing of MUC2 mucin in ulcerative colitis and in Crohn’s disease increases detectability of the MUC2 protein core. J Pathol. 1999; 188(3):304–11.
  25. Weiss A.A Babyatsky MW, Ogata S, Chen A, Itzkowitz SH. Expression of MUC2 and MUC3 mRNA in human normal, malignant, and infl ammatory intestinal tissues. J Histochem Cytochem. 1996; 44(10):1161–6.
  26. Johansson M. E., Sjövall H., Hansson G. C. Th e gastrointestinal mucus system in health and disease. Nat Rev Gastroenterol Hepatol. 2013; 10(6):352–61. doi: 10.1038/ nrgastro.2013.35
  27. Higuchi T., Orita T, Nakanishi S, Katsuya K, Watanabe H, Yamasaki Y, Waga I, Nanayama T, Yamamoto Y, Munger W, Sun HW, Falk RJ, Jennette JC, Alcorta DA, Li H, Yamamoto T, Saito Y, Nakamura M. Molecular cloning, genomic structure, and expression analysis of MUC20, a novel mucin protein, up-regulated in injured kidney. J Biol Chem. 2004; 279(3):1968–79.
  28. Longman R. J., Poulsom R, Corfield AP, Warren BF, Wright NA, Th omas MG. Alterations in the composition of the supramucosal defense barrier in relation to disease severity of ulcerative colitis. J Histochem Cytochem. 2006; 54(12):1335–48.
  29. Itoh Y., Kamata-Sakurai M, Denda-Nagai K, Nagai S, Tsuiji M, Ishii-Schrade K, Okada K, Goto A, Fukayama M, Irimura T. Identification and expression of human epiglycanin/MUC21: a novel transmembrane mucin. Glycobiology. 2008; 18(1): 74–83.
  30. Pallesen L. T., Berglund L, Rasmussen LK, Petersen TE, Rasmussen JT. Isolation and characterization of MUC15, a novel cell membrane-associated mucin. Eur J Biochem. 2002; 269(11): 2755–2763.
  31. Yamamoto-Furusho J., Ascaño-Gutiérrez I., Furuzawa- Carballeda J., Fonseca-Camarillo G. Mucin 16 (MUC16) and mucin 20 (MUC20) over-expression in colonic mucosa is associated with histological remission in patients with ulcerative colitis. J Crohns Colitis. First published online. 2014; 8(Issue Supplement 1): S139. doi: https://doi.org/10.1016/S1873–9946(14)60306–8
  32. Petersson J., Schreiber O, Hansson GC, Gendler SJ, Velcich A, Lundberg JO, Roos S, Holm L, Phillipson M. Importance and regulation of the colonic mucus barrier in a mouse model of colitis. Am J Physiol Gastrointest Liver Physiol. 2011; 300(2): G327–33. doi: 10.1152/ajpgi.00422.2010.
  33. Sheng Y. H., Lourie R, Lindén SK, Jeff ery PL, Roche D, Tran TV, Png CW, Waterhouse N, Sutton P, Florin TH, McGuckin MA. Th e MUC13 cell-surface mucin protects against intestinal infl ammation by inhibiting epithelial cell apoptosis. Gut. 2011; 60(12):1661–70. doi: 10.1136/ gut.2011.239194.
  34. Bach S. P., Renehan A. G., Potten C. S. Stem cells: the intestinal stem cell as a paradigm. Carcinogenesis. 2000; 21(3): 469–476.
  35. Ross M. H., Pawlina W. Histology: A text and atlas: with correlated cell and molecular biology. – Baltimore: MD: Lippincott Wiliams & Wilkins, 2006. 906 p.
  36. Ham A. W., Cormack D. H. Histology [Russian translation], Vol.4, Moscow.1983. 246 p.
  37. Noah T. K., Donahue B., Shroyer N. F. Intestinal development and differentiation. Exp Cell Res. 2011; 317(19):2702–10. doi: 10.1016/j.yexcr.2011.09.006.
  38. Treuting P. M., Dintzis S. M., Frevert C. W. et al. Comparative anatomy and histology: a mouse and human atlas. Amsterdam: Elsevier/Academic Press. XII, 2012. 461 p.
  39. Myllärniemi H., Nickels J. Scanning electron microscopy of Crohn’s disease and ulcerative colitis of the colon. Virchows Arch A Pathol Anat Histol. 1980; 385(3): 343–350.
  40. Barkas F., Liberopoulos E., Kei A., Elisaf M. Electrolyte and acid-base disorders in infl ammatory bowel disease // Ann Gastroenterol. 2013; 26(1): 23–28.
  41. Parfenov A. I. Infl ammatory bowel diseases in the XXI century. EkspKlinGastroenterol. 2012; (3):3–6.
  42. Gledhill A., Hall P. A., Cruse J. P., Pollock D. J. Enteroendocrine cell hyperplasia, carcinoid tumours and adenocarcinoma in long-standing ulcerative colitis. Histopathology. 1986; 10(5): 501–508.
  43. El-Salhy M., Danielsson A., Stenling R., Grimelius L. Colonic endocrine cells in infl ammatory bowel disease. J Intern Med. 1997; 242(5): 413–419.
  44. Rybakova M. G., Botina A. V., Solov’eva O.I. [Immunomorphological characteristics of mucosal and endocrine cells of the colon in patients with chronic ulcerative colitis]. Arkh Patol. 2005; 67(2): 30–33.
  45. Gunawardene A. R., Corfe B. M., Staton C. A. Classifi cation and functions of enteroendocrine cells of the lower gastrointestinal tract. Int J Exp Pathol. 2011; 92(4):219–31. doi: 10.1111/j.1365–2613.2011.00767.x.
  46. Manocha M., Khan W. I. Serotonin and GI Disorders: An Update on Clinical and Experimental Studies. Clin Transl Gastroenterol. 2012; 3: e13. doi: 10.1038/ ctg.2012.8
  47. Chen M, Gao L, Chen P, Feng D, Jiang Y, Chang Y, Jin J, Chu FF, Gao Q. Serotonin-exacerbated DSS-induced colitis is associated with increase in MMP-3 and MMP-9 expression in the mouse colon. Mediators Infl amm. 2016; 2016:5359768. doi: 10.1155/2016/5359768.
  48. Coates M. D., Mahoney CR, Linden DR, Sampson JE, Chen J, Blaszyk H, Crowell MD, Sharkey KA, Gershon MD, Mawe GM, Moses PL. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004; 126(7): 1657–1664.
  49. El-Salhy M., Mazzawi T, Gundersen D, Hatlebakk JG, Hausken T. Th e role of peptide YY in gastrointestinal diseases and disorders (review). Int J Mol Med. – 2013; 31(2):275–82. doi: 10.3892/ijmm.2012.1222.
  50. Yarilin A. A. Immunologiya: uchebnik [Immunology: a textbook]. Moscow, GEOTАR Media, 2010. 752 p.
  51. Bennett K. M., Parnell E. A., Sanscartier C. Parks S., Chen G., Nair M. G., Lo D. D. Induction of Colonic M Cells during Intestinal Infl ammation. Am J Pathol. 2016; 186(5):1166–79. doi: 10.1016/j.ajpath.2015.12.015
  52. Fratila O., Ilias T., Maghiar T. T., Puscasiu M., Puscasiu D. Ultrastructural aspects of the colonic epithelium in ulcerative colitis. Studia Universitatis “Vasile Goldiș”, Seria Ştiințele Vieţii (Life Sciences Series). 2008; 18: 215–218
  53. Groschwitz K. R., Hogan S. P. Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol. 2009; 124(1):3–20; quiz 21–2. doi: 10.1016/j.jaci.2009.05.038.
  54. Delva E., Tucker D. K., Kowalczyk A. P. Th e desmosome. Cold Spring Harb Perspect Biol. 2009; 1(2): a002543. doi: 10.1101/cshperspect.a002543.
  55. Zhang C., Liu L. W., Sun W. J., Qin S. H., Qin L. Z., Wang X. Expressions of E-cadherin, p120ctn, β-catenin and NF-κB in ulcerative colitis. J Huazhong Univ Sci Technolog Med Sci. 2015; 35(3):368–373. doi: 10.1007/ s11596–015–1439–9.
  56. Lu Z., Ding L., Lu Q., Chen Y. H. Claudins in intestines: Distribution and functional signifi cance in health and diseases. Tissue Barriers. 2013; 1(3): e24978. doi: 10.4161/tisb.24978.
  57. Günzel D., Yu A. S. Claudins and the modulation of tight junction permeability. Physiol Rev. 2013; 93(2):525–69. doi: 10.1152/physrev.00019.2012.
  58. Schmitz H., Barmeyer C., Fromm M., Runkel N, Foss HD, Bentzel CJ, Riecken EO, Schulzke JD. Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis. Gastroenterology. 1999; 116(2): 301–309.
  59. Oshima T., Miwa H., Joh T. Changes in the expression of claudins in active ulcerative colitis. J Gastroenterol Hepatol. 2008; 23 Suppl 2: S146–50. doi: 10.1111/j.1440– 1746.2008.05405.x.
  60. Brubaker S. W., Bonham K. S., Zanoni I., Kagan J. C. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol. 2015; 33:257–90. doi: 10.1146/annurev-immunol-032414–112240
  61. McClure R., Massari P. TLR-Dependent Human Mucosal Epithelial Cell Responses to Microbial Pathogens. Front Immunol. 2014; 5:386. doi: 10.3389/fi mmu.2014.00386.
  62. Peterson L. W., Artis D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol. 2014; 14(3):141–53. doi: 10.1038/ nri3608.
  63. Oswald I. P. Role of intestinal epithelial cells in the innate immune defence of the pig intestine. Vet Res. 2006; 37(3): 359–368.
  64. Bamias G., Kaltsa G., Ladas S. D. Cytokines in the Pathogenesis of Ulcerative Colitis. Discov Med. 2011; 11(60): 459–467.

Для цитирования:
Золотова Н. А., Архиева Х. М., Зайратьянц О. В. Эпителиальный барьер толстой кишки в норме и при язвенном колите. Экспериментальная и клиническая гастроэнтерология. 2019;162(2): 4–13. DOI: 10.31146/1682-8658-ecg-162-2-4-13
Загрузить полный текст