Research progress of tumor necrosis factor α / c-Jun N-terminal kinase / mucin 2 in intestinal barrier dysfunction_West China Medical Journal

Authors：

AMANGULI Moming ^1,2 , ZHANG Qi ² , AISHANJIANG Rouzi ² , JIANG Mengna ² ,  SONG Yunlin ²

1. Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China;
2. Center of Critical Care Medicine, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P. R. China;

Corresponding author：

SONG Yunlin, Email: 17929294@qq.com

Keywords：

Intestinal barrier; mucin 2; tumor necrosis factor-α; c-jun N-terminal kinase signaling pathway

DOI：

10.7507/1002-0179.202303192

Video：

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The gut mucus barrier and mechanical barrier are the most important natural barriers, the former is the first defense barrier, which separates pathogenic bacteria in intestinal lumen from the epithelial cells, and prevents them passing through the intestinal barrier into the human circulation system. Studies have shown that inflammation in the body affects the content of mucin 2, a key protein in the mucus layer, thereby changing the permeability of the mucus barrier and promoting the translocation of pathogenic microorganisms. Both tumor necrosis factor-α and c-jun N-terminal kinase signaling pathways have been reported to be closely related to the occurrence and development of inflammation. Therefore, this article reviews the relationship between tumor necrosis factor-α, c-jun N-terminal kinase signaling pathway and mucin 2 and intestinal barrier dysfunction, in order to provide new ideas and directions for exploring the related research of intestinal barrier function.

Citation： AMANGULI Moming, ZHANG Qi, AISHANJIANG Rouzi, JIANG Mengna, SONG Yunlin. Research progress of tumor necrosis factor α / c-Jun N-terminal kinase / mucin 2 in intestinal barrier dysfunction. West China Medical Journal, 2023, 38(8): 1257-1261. doi: 10.7507/1002-0179.202303192 Copy

1.	Ahn DH, Crawley SC, Hokari R, et al. TNF-alpha activates MUC2 transcription via NF-kappaB but inhibits via JNK activation. Cell Physiol Biochem, 2005, 15(1/2/3/4): 29-40.
2.	刘静, 高颖, 杨利, 等. 知母-黄芪散复方通过 TNF-α/JNK 通路改善阿尔茨海默症大鼠认知障碍的研究. 中药新药与临床药理, 2017, 28(3): 320-326.
3.	Yao D, Dai W, Dong M, et al. MUC2 and related bacterial factors: therapeutic targets for ulcerative colitis. EBioMedicine, 2021, 74: 103751.
4.	Jiang L, Feng J, Ying R, et al. Individual and combined effects of ammonia-N and sulfide on the immune function and intestinal microbiota of pacific white shrimp litopenaeus vannamei. Fish Shellfish Immunol, 2019, 92: 230-240.
5.	Xie S, Zhao S, Jiang L, et al. Lactobacillus reuteri stimulates intestinal epithelial proliferation and induces differentiation into goblet cells in young chickens. J Agric Food Chem, 2019, 67(49): 13758-13766.
6.	Feng L, Chen S, Zhang L, et al. Bisphenol A increases intestinal permeability through disrupting intestinal barrier function in mice. Environ Pollut, 2019, 254(Pt A): 112960.
7.	Wells JM, Brummer RJ, Derrien M, et al. Homeostasis of the gut barrier and potential biomarkers. Am J Physiol Gastrointest Liver Physiol, 2017, 312(3): G171-G193.
8.	Capaldo CT, Powell DN, Kalman D. Layered defense: how mucus and tight junctions seal the intestinal barrier. J Mol Med (Berl), 2017, 95(9): 927-934.
9.	Okumura R, Takeda K. Maintenance of intestinal homeostasis by mucosal barriers. Inflamm Regen, 2018, 38: 5.
10.	Cheng L, Kong C, Walvoort MTC, et al. Human milk oligosaccharides differently modulate goblet cells under homeostatic, proinflammatory conditions and ER stress. Mol Nutr Food Res, 2020, 64(5): e1900976.
11.	Nyström EEL, Martinez-Abad B, Arike L, et al. An intercrypt subpopulation of goblet cells is essential for colonic mucus barrier function. Science, 2021, 372(6539): eabb1590.
12.	Vancamelbeke M, Vanuytsel T, Farré R, et al. Genetic and transcriptomic bases of intestinal epithelial barrier dysfunction in inflammatory bowel disease. Inflamm Bowel Dis, 2017, 23(10): 1718-1729.
13.	Qin T, Yang J, Huang D, et al. DOCK4 stimulates MUC2 production through its effect on goblet cell differentiation. J Cell Physiol, 2021, 236(9): 6507-6519.
14.	Johansson ME, Hansson GC. Immunological aspects of intestinal mucus and mucins. Nat Rev Immunol, 2016, 16(10): 639-649.
15.	Kawakami S, Ito R, Maruki-Uchida H, et al. Intake of a mixture of sake cake and rice malt increases mucin levels and changes in intestinal microbiota in mice. Nutrients, 2020, 12(2): 449.
16.	Stremmel W, Vural H, Evliyaoglu O, et al. Delayed-release phosphatidylcholine is effective for treatment of ulcerative colitis: a meta- analysis. Dig Dis, 2021, 39(5): 508-515.
17.	Feofanova NA, Bets VD, Borisova MA, et al. L-fucose reduces gut inflammation due to T-regulatory response in Muc2 null mice. PLoS One, 2022, 17(12): e0278714.
18.	Qu L, Lin X, Liu C, et al. Atractylodin attenuates dextran sulfate sodium-induced colitis by alleviating gut microbiota dysbiosis and inhibiting inflammatory response through the MAPK pathway. Front Pharmacol, 2021, 12: 665376.
19.	Li J, Zhang L, Wu T, et al. Indole-3-propionic acid improved the intestinal barrier by enhancing epithelial barrier and mucus barrier. J Agric Food Chem, 2021, 69(5): 1487-1495.
20.	Engevik MA, Luk B, Chang-Graham AL, et al. Bifidobacterium dentium Fortifies the Intestinal Mucus Layer via Autophagy and Calcium Signaling Pathways. mBio, 2019, 10(3): e01087-19.
21.	Javitt G, Khmelnitsky L, Albert L, et al. Assembly mechanism of mucin and von willebrand factor polymers. Cell, 2020, 183(3): 717-729. e16.
22.	Harrison CA, Laubitz D, Ohland CL, et al. Microbial dysbiosis associated with impaired intestinal Na⁺/H⁺ exchange accelerates and exacerbates colitis in ex-germ free mice. Mucosal Immunol, 2018, 11(5): 1329-1341.
23.	Demouveaux B, Gouyer V, Gottrand F, et al. Gel-forming mucin interactome drives mucus viscoelasticity. Adv Colloid Interface Sci, 2018, 252: 69-82.
24.	Bergstrom K, Fu J, Johansson ME, et al. Core 1- and 3- derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice. Mucosal Immunol, 2017, 10(1): 91-103.
25.	Schroeder BO, Birchenough GMH, Ståhlman M, et al. Bifidobacteria or fiber protects against diet-induced microbiota-mediated colonic mucus deterioration. Cell Host Microbe, 2018, 23(1): 27-40. e7.
26.	Kawahara T, Makizaki Y, Oikawa Y, et al. Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors. PLoS One, 2017, 12(3): e0173979.
27.	Nagpal R, Kurakawa T, Tsuji H, et al. Evolution of gut bifidobacterium population in healthy Japanese infants over the first three years of life: a quantitative assessment. Sci Rep, 2017, 7(1): 10097.
28.	Xie X, Zhou J, Hu L, et al. Exposure to hexafluoropropylene oxide dimer acid (HFPO-DA) disturbs the gut barrier function and gut microbiota in mice. Environ Pollut, 2021, 290: 117934.
29.	Li C, Zuo D, Yin L, et al. Prognostic Value of MUC2 expression in colorectal cancer: a systematic review and meta-analysis. Gastroenterol Res Pract, 2018, 2018: 6986870.
30.	Gundamaraju R, Chong WC. Consequence of distinctive expression of MUC2 in colorectal cancers: how much is actually bad?. Biochim Biophys Acta Rev Cancer, 2021, 1876(1): 188579.
31.	Khandakar H, Agarwal S, Sharma MC, et al. Amphicrine medullary thyroid carcinoma - a case-based review expanding on its MUC expression profile. Endocr Pathol, 2022, 33(3): 378-387.
32.	Al-Shaibi AA, Abdel-Motal UM, Hubrack SZ, et al. Human AGR2 deficiency causes mucus barrier dysfunction and infantile inflammatory bowel disease. Cell Mol Gastroenterol Hepatol, 2021, 12(5): 1809-1830.
33.	Leon-Coria A, Kumar M, Workentine M, et al. Muc2 mucin and nonmucin microbiota confer distinct innate host defense in disease susceptibility and colonic injury. Cell Mol Gastroenterol Hepatol, 2021, 11(1): 77-98.
34.	Duan Y, Liu Q, Wang Y, et al. Impairment of the intestine barrier function in litopenaeus vannamei exposed to ammonia and nitrite stress. Fish Shellfish Immunol, 2018, 78: 279-288.
35.	Gonzalez A, Krieg R, Massey HD, et al. Sodium butyrate ameliorates insulin resistance and renal failure in CKD rats by modulating intestinal permeability and mucin expression. Nephrol Dial Transplant, 2019, 34(5): 783-794.
36.	Balda MS, Matter K. Tight junctions at a glance. J Cell Sci, 2008, 121(Pt 22): 3677-3682.
37.	Ruder B, Atreya R, Becker C. Tumour Necrosis Factor Alpha in Intestinal Homeostasis and Gut Related Diseases. Int J Mol Sci, 2019, 20(8): 1887.
38.	Khan I, Huang Z, Liang L, et al. Ammonia stress influences intestinal histomorphology, immune status and microbiota of Chinese striped-neck turtle (mauremys sinensis). Ecotoxicol Environ Saf, 2021, 222: 112471.

1. Ahn DH, Crawley SC, Hokari R, et al. TNF-alpha activates MUC2 transcription via NF-kappaB but inhibits via JNK activation. Cell Physiol Biochem, 2005, 15(1/2/3/4): 29-40.
2. 刘静, 高颖, 杨利, 等. 知母-黄芪散复方通过 TNF-α/JNK 通路改善阿尔茨海默症大鼠认知障碍的研究. 中药新药与临床药理, 2017, 28(3): 320-326.
3. Yao D, Dai W, Dong M, et al. MUC2 and related bacterial factors: therapeutic targets for ulcerative colitis. EBioMedicine, 2021, 74: 103751.
4. Jiang L, Feng J, Ying R, et al. Individual and combined effects of ammonia-N and sulfide on the immune function and intestinal microbiota of pacific white shrimp litopenaeus vannamei. Fish Shellfish Immunol, 2019, 92: 230-240.
5. Xie S, Zhao S, Jiang L, et al. Lactobacillus reuteri stimulates intestinal epithelial proliferation and induces differentiation into goblet cells in young chickens. J Agric Food Chem, 2019, 67(49): 13758-13766.
6. Feng L, Chen S, Zhang L, et al. Bisphenol A increases intestinal permeability through disrupting intestinal barrier function in mice. Environ Pollut, 2019, 254(Pt A): 112960.
7. Wells JM, Brummer RJ, Derrien M, et al. Homeostasis of the gut barrier and potential biomarkers. Am J Physiol Gastrointest Liver Physiol, 2017, 312(3): G171-G193.
8. Capaldo CT, Powell DN, Kalman D. Layered defense: how mucus and tight junctions seal the intestinal barrier. J Mol Med (Berl), 2017, 95(9): 927-934.
9. Okumura R, Takeda K. Maintenance of intestinal homeostasis by mucosal barriers. Inflamm Regen, 2018, 38: 5.
10. Cheng L, Kong C, Walvoort MTC, et al. Human milk oligosaccharides differently modulate goblet cells under homeostatic, proinflammatory conditions and ER stress. Mol Nutr Food Res, 2020, 64(5): e1900976.
11. Nyström EEL, Martinez-Abad B, Arike L, et al. An intercrypt subpopulation of goblet cells is essential for colonic mucus barrier function. Science, 2021, 372(6539): eabb1590.
12. Vancamelbeke M, Vanuytsel T, Farré R, et al. Genetic and transcriptomic bases of intestinal epithelial barrier dysfunction in inflammatory bowel disease. Inflamm Bowel Dis, 2017, 23(10): 1718-1729.
13. Qin T, Yang J, Huang D, et al. DOCK4 stimulates MUC2 production through its effect on goblet cell differentiation. J Cell Physiol, 2021, 236(9): 6507-6519.
14. Johansson ME, Hansson GC. Immunological aspects of intestinal mucus and mucins. Nat Rev Immunol, 2016, 16(10): 639-649.
15. Kawakami S, Ito R, Maruki-Uchida H, et al. Intake of a mixture of sake cake and rice malt increases mucin levels and changes in intestinal microbiota in mice. Nutrients, 2020, 12(2): 449.
16. Stremmel W, Vural H, Evliyaoglu O, et al. Delayed-release phosphatidylcholine is effective for treatment of ulcerative colitis: a meta- analysis. Dig Dis, 2021, 39(5): 508-515.
17. Feofanova NA, Bets VD, Borisova MA, et al. L-fucose reduces gut inflammation due to T-regulatory response in Muc2 null mice. PLoS One, 2022, 17(12): e0278714.
18. Qu L, Lin X, Liu C, et al. Atractylodin attenuates dextran sulfate sodium-induced colitis by alleviating gut microbiota dysbiosis and inhibiting inflammatory response through the MAPK pathway. Front Pharmacol, 2021, 12: 665376.
19. Li J, Zhang L, Wu T, et al. Indole-3-propionic acid improved the intestinal barrier by enhancing epithelial barrier and mucus barrier. J Agric Food Chem, 2021, 69(5): 1487-1495.
20. Engevik MA, Luk B, Chang-Graham AL, et al. Bifidobacterium dentium Fortifies the Intestinal Mucus Layer via Autophagy and Calcium Signaling Pathways. mBio, 2019, 10(3): e01087-19.
21. Javitt G, Khmelnitsky L, Albert L, et al. Assembly mechanism of mucin and von willebrand factor polymers. Cell, 2020, 183(3): 717-729. e16.
22. Harrison CA, Laubitz D, Ohland CL, et al. Microbial dysbiosis associated with impaired intestinal Na⁺/H⁺ exchange accelerates and exacerbates colitis in ex-germ free mice. Mucosal Immunol, 2018, 11(5): 1329-1341.
23. Demouveaux B, Gouyer V, Gottrand F, et al. Gel-forming mucin interactome drives mucus viscoelasticity. Adv Colloid Interface Sci, 2018, 252: 69-82.
24. Bergstrom K, Fu J, Johansson ME, et al. Core 1- and 3- derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice. Mucosal Immunol, 2017, 10(1): 91-103.
25. Schroeder BO, Birchenough GMH, Ståhlman M, et al. Bifidobacteria or fiber protects against diet-induced microbiota-mediated colonic mucus deterioration. Cell Host Microbe, 2018, 23(1): 27-40. e7.
26. Kawahara T, Makizaki Y, Oikawa Y, et al. Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors. PLoS One, 2017, 12(3): e0173979.
27. Nagpal R, Kurakawa T, Tsuji H, et al. Evolution of gut bifidobacterium population in healthy Japanese infants over the first three years of life: a quantitative assessment. Sci Rep, 2017, 7(1): 10097.
28. Xie X, Zhou J, Hu L, et al. Exposure to hexafluoropropylene oxide dimer acid (HFPO-DA) disturbs the gut barrier function and gut microbiota in mice. Environ Pollut, 2021, 290: 117934.
29. Li C, Zuo D, Yin L, et al. Prognostic Value of MUC2 expression in colorectal cancer: a systematic review and meta-analysis. Gastroenterol Res Pract, 2018, 2018: 6986870.
30. Gundamaraju R, Chong WC. Consequence of distinctive expression of MUC2 in colorectal cancers: how much is actually bad?. Biochim Biophys Acta Rev Cancer, 2021, 1876(1): 188579.
31. Khandakar H, Agarwal S, Sharma MC, et al. Amphicrine medullary thyroid carcinoma - a case-based review expanding on its MUC expression profile. Endocr Pathol, 2022, 33(3): 378-387.
32. Al-Shaibi AA, Abdel-Motal UM, Hubrack SZ, et al. Human AGR2 deficiency causes mucus barrier dysfunction and infantile inflammatory bowel disease. Cell Mol Gastroenterol Hepatol, 2021, 12(5): 1809-1830.
33. Leon-Coria A, Kumar M, Workentine M, et al. Muc2 mucin and nonmucin microbiota confer distinct innate host defense in disease susceptibility and colonic injury. Cell Mol Gastroenterol Hepatol, 2021, 11(1): 77-98.
34. Duan Y, Liu Q, Wang Y, et al. Impairment of the intestine barrier function in litopenaeus vannamei exposed to ammonia and nitrite stress. Fish Shellfish Immunol, 2018, 78: 279-288.
35. Gonzalez A, Krieg R, Massey HD, et al. Sodium butyrate ameliorates insulin resistance and renal failure in CKD rats by modulating intestinal permeability and mucin expression. Nephrol Dial Transplant, 2019, 34(5): 783-794.
36. Balda MS, Matter K. Tight junctions at a glance. J Cell Sci, 2008, 121(Pt 22): 3677-3682.
37. Ruder B, Atreya R, Becker C. Tumour Necrosis Factor Alpha in Intestinal Homeostasis and Gut Related Diseases. Int J Mol Sci, 2019, 20(8): 1887.
38. Khan I, Huang Z, Liang L, et al. Ammonia stress influences intestinal histomorphology, immune status and microbiota of Chinese striped-neck turtle (mauremys sinensis). Ecotoxicol Environ Saf, 2021, 222: 112471.

West China Medical Journal

Research progress of tumor necrosis factor α / c-Jun N-terminal kinase / mucin 2 in intestinal barrier dysfunction

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