Tanzhou Chen1, Haibo Xue2, Ruoyang Lin2, Zhiming Huang2. 1. The Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: cctzz@163.com. 2. The Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Abstract
BACKGROUND: Aberrant expression of miRNAs was a critical element in the pathogenesis of inflammatory bowel disease (IBD). This study aimed to explore the involvement and mechanism of miR-126 in IBD. METHODS: In this study, the endogenous expressions of miR-126, S1PR2 and S1P in the pathological tissues of patients with IBD were detected using qRT-PCR and western blot assay, respectively. The luciferase reporter gene assay was performed to confirm the targeting regulatory relation between miR-126 and S1PR2. The transendothelial electrical resistance assay was used to measured the value of TEER. RESULTS: The expressions of miR-126, S1PR2 and S1P in the pathological tissues of IBD patients were significantly higher than that of the control group. Moreover, miR-126 overexpression contributed to intestinal mucosal barrier dysfunction in vitro. S1PR2 was a direct target of miR-126, and S1PR2 expression was negatively regulated by miR-126 in Caco-2 cells. However, S1PR2 activated by S1P had the protection effect for the integrity and permeability of intestinal mucosal barrier via a PI3K/Akt dependent mechanism. MiR-126 silencing possessed obvious protective effects on the intestinal barrier function, but these effects could be reversed by JTE-013 or LY294002. CONCLUSION: MiR-126 down-regulated S1PR2 and then prevented the activation of PI3K/AKT signaling pathway, which ultimately could damage intestinal mucosal barrier function.
BACKGROUND: Aberrant expression of miRNAs was a critical element in the pathogenesis of inflammatory bowel disease (IBD). This study aimed to explore the involvement and mechanism of miR-126 in IBD. METHODS: In this study, the endogenous expressions of miR-126, S1PR2 and S1P in the pathological tissues of patients with IBD were detected using qRT-PCR and western blot assay, respectively. The luciferase reporter gene assay was performed to confirm the targeting regulatory relation between miR-126 and S1PR2. The transendothelial electrical resistance assay was used to measured the value of TEER. RESULTS: The expressions of miR-126, S1PR2 and S1P in the pathological tissues of IBDpatients were significantly higher than that of the control group. Moreover, miR-126 overexpression contributed to intestinal mucosal barrier dysfunction in vitro. S1PR2 was a direct target of miR-126, and S1PR2 expression was negatively regulated by miR-126 in Caco-2 cells. However, S1PR2 activated by S1P had the protection effect for the integrity and permeability of intestinal mucosal barrier via a PI3K/Akt dependent mechanism. MiR-126 silencing possessed obvious protective effects on the intestinal barrier function, but these effects could be reversed by JTE-013 or LY294002. CONCLUSION:MiR-126 down-regulated S1PR2 and then prevented the activation of PI3K/AKT signaling pathway, which ultimately could damage intestinal mucosal barrier function.
Authors: Alexander L Ticho; Pooja Malhotra; Pradeep K Dudeja; Ravinder K Gill; Waddah A Alrefai Journal: Compr Physiol Date: 2019-12-18 Impact factor: 9.090
Authors: Suruchi K Batra; Christopher R Heier; Lina Diaz-Calderon; Christopher B Tully; Alyson A Fiorillo; John van den Anker; Laurie S Conklin Journal: Inflamm Bowel Dis Date: 2020-09-18 Impact factor: 5.325