Raf kinase inhibitor protein mediates intestinal epithelial cell apoptosis and promotes IBDs in humans and mice

Gut
Wenlong LinXiaojian Wang

Abstract

Raf kinase inhibitor protein (RKIP) appears to control cancer cell metastasis and its expression in colonic tissue is related to colonic cancer development. We sought to identify the roles of RKIP in maintaining homeostasis of GI tract. The expression of RKIP was determined by immunohistochemistry and western blot analysis. RKIP knockout and wild-type mice were administered dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis, and the mice were assessed based on colitis symptoms and biochemical approaches. The mechanism was analysed using immunoprecipitation and pull-down experiments. The RKIP expression is positively correlated with the severity of IBD. RKIP deficiency protects mice from DSS-induced or TNBS-induced colitis and accelerated recovery from colitis. RKIP deficiency inhibits DSS-induced infiltration of acute-phase immune cells and reduces production of proinflammatory cytokines and chemokines in colon. RKIP deficiency inhibits DSS-induced or TNBS-induced colonic epithelial barrier damage and intestinal epithelial cell (IEC) apoptosis. RKIP deficiency also inhibits tumour necrosis factor-alpha-induced IEC apoptosis and colitis. Mechanistically, RKIP enhances the ind...Continue Reading

Citations

Feb 24, 2017·Cell Death & Disease·Michael A SchumacherMark R Frey
Nov 27, 2019·Biomolecules·Maria Gabriela-FreitasOlga Martinho
Jun 17, 2020·Experimental and Therapeutic Medicine·Lei ZhuJia-Fei Cheng
Sep 10, 2020·Cellular & Molecular Immunology·Qiang QinXiaojian Wang
Apr 26, 2017·Proceedings of the National Academy of Sciences of the United States of America·Yongfeng LiuJun Qin
Feb 6, 2018·Cellular & Molecular Immunology·Zhaoru ZhangJun Zhou
Oct 5, 2018·Proceedings of the National Academy of Sciences of the United States of America·Wenlong LinXiaojian Wang
Apr 16, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rongrong LaiXiaojian Wang
May 15, 2021·Journal of Crohn's & Colitis·Lijuan WangQifeng Yang

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