The morphofunctional profile of a mouse model of acute moderate dextran sodium sulfate-induced colitis
N. A. Zolotova,
M. V. Kirillova,
I. S. Tsvetkov,
D. Sh. Dzhalilova,
L. V. Ozeretskaya,
M. T. Dobrynina,
O. V. Makarova https://doi.org/10.55959/MSU0137-0952-16-80-3-2
Abstract
Ulcerative colitis is a socially significant disease, but its etiology is unclear. The most widely used experimental model is dextran sodium sulfate (DSS)-induced colitis. The aim of the work was to characterize morphofunctional and molecular biological changes in the colon and mesenteric lymph nodes in acute colitis induced by 1% DSS solution in male C57BL/6 mice. Upon induction of colitis, moderate ulcerative inflammatory process developed in the colon, hyperplasia of the cortex, plasmatization of the medullary cords and macrophage reaction in the sinuses were observed in the mesenteric lymph nodes. Inflammatory infiltration, increased macrophage content, decreased volume fraction of goblet cells and neutral mucin content in them, increased endocrine cell content, increased expression of Cldn4, Cldn7, Bax and Bcl2 were detected in the colon. Pronounced changes in the composition of intestinal microflora were observed.
Keywords
ulcerative colitis,
experimental colitis,
dextran sulfate sodium,
microflora, biological model,
inflammation
Supporting agencies: This study was performed under the state assignment of Petrovsky National Research Center of Surgery, project no. 122030200530-6.
About the Authors
N. A. Zolotova
Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery
Russian Federation
Russian Federation
3 Tsyurupa Str., Moscow, 117418
M. V. Kirillova
Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery
Russian Federation
Russian Federation
3 Tsyurupa Str., Moscow, 117418
I. S. Tsvetkov
Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery
Russian Federation
Russian Federation
3 Tsyurupa Str., Moscow, 117418
D. Sh. Dzhalilova
Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery
Russian Federation
Russian Federation
3 Tsyurupa Str., Moscow, 117418
L. V. Ozeretskaya
Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery
Russian Federation
Russian Federation
3 Tsyurupa Str., Moscow, 117418
M. T. Dobrynina
Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery;
Department of Cell Biology and Histology, Faculty of Biology, Lomonosov Moscow State University
Russian Federation
Russian Federation
3 Tsyurupa Str., Moscow, 117418
1–12 Leninskie Gory, Moscow, 119234
O. V. Makarova
Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery;
Department of Cell Biology and Histology, Faculty of Biology, Lomonosov Moscow State University
Russian Federation
Russian Federation
3 Tsyurupa Str., Moscow, 117418
1–12 Leninskie Gory, Moscow, 119234
References
1. Маркова А.А., Кашкина Е.И. Современные методы диагностики и оценки тяжести течения неспецифического язвенного колита. Вестник ТГУ. 2012;17(3):915–919.
2. Du L., Ha C. Epidemiology and pathogenesis of ulcerative colitis. Gastroenterol. Clin. North Am. 2020;49(4):643–654.
3. Bolotova E.V., Yumukyan K.A., Dudnikova A.V. Modern idea of the mechanisms of development and predictors of ulcerative colitis severity. Doctor.Ru. 2022;21(2):34–39.
4. Золотова Н.А., Архиева Х.М., Зайратьянц О.В. Эпителиальный барьер толстой кишки в норме и при язвенном колите. Экспер. клин. гастроэнтерол. 2019;(2):4–13.
5. Katsandegwaza B., Horsnell W., Smith K. Inflammatory bowel disease: a review of pre-clinical murine models of human disease. Int. J. Mol. Sci. 2022;23(16):9344.
6. Sann H., Erichsen J.V., Hessmann M., Pahl A., Hoffmeyer A. Efficacy of drugs used in the treatment of IBD and combinations thereof in acute DSS-induced colitis in mice. Life Sci. 2013;92(12):708–718.
7. Postovalova E.A., Khochansky D.N., Zolotova N.A., Gao Y., Makarova O.V., Dobrynina M.T. Morphological changes in mesenteric lymph nodes and lymphocyte subpopulation composition in experimental ulcerative colitis. Bull. Exp. Biol. Med. 2016;160(6):835–839.
8. Дорофеев А.Э., Василенко И.В., Рассохина О.А. Изменения экспрессии MUC2, MUC3, MUC4, TFF3 в слизистой оболочке толстого кишечника у больных неспецифическим язвенным колитом. Гастроэнтерол. 2013;47(1):80–84.
9. Issa C.M., Hambly B.D., Wang Y., Maleki S., Wang W., Fei J., Bao S. TRPV2 in the development of experimental colitis. Scand. J. Immunol. 2014;80(5):307–312.
10. Portela-Gomes G.M., Stridsberg M. Chromogranin A in the human gastrointestinal tract: an immunocytochemical study with region-specific antibodies. J. Histochem. Cytochem. 2002;50(11):1487–1492.
11. Engelstoft M.S., Lund M.L., Grunddal K.V., Egerod K.L., Osborne-Lawrence S., Poulsen S.S., Zigman J.M., Schwartz T.W. Research resource: a chromogranin A reporter for serotonin and histamine secreting enteroendocrine cells. Mol. Endocrinol. 2015;29(11):1658–1671.
12. Na Y.R., Stakenborg M., Seok S.H., Matteoli G. Macrophages in intestinal inflammation and resolution: a potential therapeutic target in IBD. Nat. Rev. Gastroenterol. Hepatol. 2019;16(9):531–543.
13. Jang S., Jang S., Ko J., Bae J.E., Hyung H., Park J.Y., Lim S.G., Park S., Park S., Yi J., Kim S., Kim M.O., Cho D.H., Ryoo Z.Y. HSPA9 reduction exacerbates symptoms and cell death in DSS-induced inflammatory colitis. Sci. Rep. 2024;14(1):5908
14. Longman R.J., Poulsom R., Corfield A.P., Warren B.F., Wright N.A., Thomas M.G. Alterations in the composition of the supramucosal defense barrier in relation to disease severity of ulcerative colitis. J. Histochem. Cytochem. 2006;54(12):1335–1348.
15. Hoebler C., Gaudier E., De Coppet P., Rival M., Cherbut C. MUC genes are differently expressed during onset and maintenance of inflammation in dextran sodium sulfate-treated mice. Dig. Dis. Sci. 2006;51(2):381–389.
16. Zolotova N.A., Polikarpova A.V., Khochanskii D.N., Makarova O.V., Mikhailova L.P. Expression of mucins and claudins in the colon during acute and chronic experimental colitis. Bull. Exp. Biol. Med. 2018;165(4):434–437.
17. Das P., Goswam P., Das T.K., Nag T., Sreenivas V., Ahuja V., Panda S.K., Gupta S.D., Makharia G.K. Comparative tight junction protein expressions in colonic Crohn’s disease, ulcerative colitis, and tuberculosis: a new perspective. Virchows Arch. 2012;460(3):261–270.
18. Oshima T., Miwa H., Joh T. Changes in the expression of claudins in active ulcerative colitis. J. Gastroenterol. Hepatol. 2008;23 Suppl. 2:S146–S150.
19. Prasad S., Mingrino R., Kaukinen K., Hayes K.L., Powell R.M., MacDonald T.T., Collins J.E. Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells. Lab. Invest. 2005;85(9):1139–1162.
20. Weber C.R., Nalle S.C., Tretiakova M., Rubin D.T., Turner J.R. Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformation. Lab. Invest. 2008;88(10):1110–1120.
21. Randall K., Henderson N., Reens J., Eckersley S., Nyström A.C., South M.C., Balendran C.A., Böttcher G., Hughes G., Price S.A. Claudin-2 expression levels in ulcerative colitis: development and validation of an in-situ hybridisation assay for therapeutic studies. PLoS One. 2016;11(9):e0162076.
22. Čužić S., Antolić M., Ognjenović A., Stupin-Polančec D., Petrinić Grba A., Hrvačić B., Dominis Kramarić M., Musladin S., Požgaj L., Zlatar I., Polančec D., Aralica G., Banić M., Urek M., Mijandrušić Sinčić B., Čubranić A., Glojnarić I., Bosnar M., Eraković Haber V. Claudins: beyond tight junctions in human IBD and murine models. Front. Pharmacol. 2021;12:682614.
23. Liu S., Wang Z., Xiang Q., Wu B., Lv W., Xu S. A comparative study in healthy and diabetic mice followed the exposure of polystyrene microplastics: Differential lipid metabolism and inflammation reaction. Ecotoxicol. Environ. Saf. 2022;244:114031.
24. Al-Failakawi A., Al-Jarallah A., Rao M., Khan I. The role of claudins in the pathogenesis of dextran sulfate sodium-induced experimental colitis: the effects of nobiletin. Biomolecules. 2024;14(9):1122.
25. Kim H.Y., Jeon H., Bae C.H., Lee Y., Kim H., Kim S. Rumex japonicus Houtt. alleviates dextran sulfate sodium-induced colitis by protecting tight junctions in mice. Integr. Med. Res. 2020;9(2):100398.
26. Yuan B., Zhou S., Lu Y., Liu J., Jin X., Wan H., Wang F. Changes in the expression and distribution of claudins, increased epithelial apoptosis, and a mannan-binding lectin-associated immune response lead to barrier dysfunction in dextran sodium sulfate-induced rat colitis. Gut Liver. 2015;9(6):734–740.
27. Золотова Н.А., Поликарпова А.В., Хочанский Д.Н., Макарова О.В., Михайлова Л.П. Экспрессия муцинов и клаудинов в ободочной кишке при остром и хроническом экспериментальном колите. Бюлл. эксп. биол. мед. 2018;165(4):421–424.
28. Nishida M., Yoshida M., Nishiumi S., Furuse M., Azuma T. Claudin-2 regulates colorectal inflammation via myosin light chain kinase-dependent signaling. Dig. Dis. Sci. 2013;58(6):1546–1559.
29. Ahmad R., Chaturvedi R., Olivares-Villagómez D., Habib T., Asim M., Shivesh P., Polk D.B., Wilson K.T., Washington M.K., Van Kaer L., Dhawan P., Singh A.B. Targeted colonic claudin-2 expression renders resistance to epithelial injury, induces immune suppression, and protects from colitis. Mucosal Immunol. 2014;7(6):1340–1353.
30. Lameris A.L., Huybers S., Kaukinen K., Mäkelä T.H., Bindels R.J., Hoenderop J.G., Nevalainen P.I. Expression profiling of claudins in the human gastrointestinal tract in health and during inflammatory bowel disease. Scand. J. Gastroenterol. 2013;48(1):58–69.
31. Cai L., Li X., Geng C., Lei X., Wang C. Molecular mechanisms of somatostatin-mediated intestinal epithelial barrier function restoration by upregulating claudin-4 in mice with DSS-induced colitis. Am. J. Physiol. Cell Physiol. 2018;315(4):C527–C536.
32. Mennigen R., Nolte K., Rijcken E., Utech M., Loeffler B., Senninger N., Bruewer M. Probiotic mixture VSL#3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 2009;296(5):G1140–G1149.
33. Arinno A., Sukmak P., Kulworasreth P., Sricharunrat T., Vaddhanaphuti C.S., Pongkorpsakol P. Gallic acid serves as an effective therapeutic agent of inflammatory bowel disease: pharmacological impacts on tight junction-dependent intestinal permeability in vivo and its related intracellular signaling. Curr. Res. Pharmacol. Drug Discov. 2025;8:100223.
34. Capaldo C.T. Claudin barriers on the brink: how conflicting tissue and cellular priorities drive IBD pathogenesis. Int. J. Mol. Sci. 2023; 24(10):8562.
35. Wang K., Ding Y., Xu C., Hao M., Li H., Ding L. Cldn-7 deficiency promotes experimental colitis and associated carcinogenesis by regulating intestinal epithelial integrity. Oncoimmunology. 2021;10(1):1923910.
36. Ogata M., Ogita T., Tari H., Arakawa T., Suzuki T. Supplemental psyllium fibre regulates the intestinal barrier and inflammation in normal and colitic mice. Br. J. Nutr. 2017;118(9):661–672.
37. Ding Y., Wang K., Xu C., Hao M., Li H., Ding L. Intestinal Claudin-7 deficiency impacts the intestinal microbiota in mice with colitis. BMC Gastroenterol. 2022;22(1):24.
38. Dvornikova K.A., Platonova O.N., Bystrova E.Y. Hypoxia and intestinal inflammation: common molecular mechanisms and signaling pathways. Int. J. Mol. Sci. 2023;24(3):2425.
39. Zong W., Friedman E.S., Allu S.R., Firrman J., Tu V., Daniel S.G., Bittinger K., Liu L., Vinogradov S.A., Wu G.D. Disruption of intestinal oxygen balance in acute colitis alters the gut microbiome. Gut Microbes. 2024;16(1):2361493.
40. Hong D., Kim H.K., Yang W., Yoon C., Kim M., Yang C.S., Yoon S. Integrative analysis of single-cell RNAseq and gut microbiome metabarcoding data elucidates macrophage dysfunction in mice with DSS-induced ulcerative colitis. Commun. Biol. 2024;7(1):731.
41. Gevers D., Kugathasan S., Denson L.A., et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe. 2014;15(3):382–392.
42. Mirsepasi-Lauridsen H.C., Vrankx K., Engberg J., Friis-Møller A., Brynskov J., Nordgaard-Lassen I., Petersen A.M., Krogfelt K.A. Disease-specific enteric microbiome dysbiosis in inflammatory bowel disease. Front. Med. (Lausanne). 2018;5:304.
Review
For citations:
Zolotova N.A., Kirillova M.V., Tsvetkov I.S., Dzhalilova D.Sh., Ozeretskaya L.V., Dobrynina M.T., Makarova O.V. The morphofunctional profile of a mouse model of acute moderate dextran sodium sulfate-induced colitis. Vestnik Moskovskogo universiteta. Seriya 16. Biologiya. 2025;80(3):156-164. (In Russ.) https://doi.org/10.55959/MSU0137-0952-16-80-3-2
Views:
15
Email this article 