title: MiR-126 impairs the intestinal barrier function via inhibiting S1PR2 mediated activation of PI3K/AKT signaling pathway.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  MiR-126 down-regulated S1PR2 and then prevented the activation of PI3K/AKT signaling pathway, which ultimately could damage intestinal mucosal barrier function.
authors.affiliation: The Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: cctzz@163.com.
authors.forename: Tanzhou
authors.initials: T
authors.lastname: Chen
authors.affiliation: The Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Xue
authors.affiliation: The Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
authors.forename: Ruoyang
authors.initials: R
authors.lastname: Lin
authors.affiliation: The Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Huang
mesh_terms: D018938:Caco-2 Cells; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000502:physiology*; D035683:MicroRNAs / Q000378:metabolism*; D010539:Permeability; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000081025:Sphingosine-1-Phosphate Receptors
chemical_list: D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D049349:Receptors, Lysosphingolipid; D000081025:Sphingosine-1-Phosphate Receptors; C527111:MIRN126 microRNA, human; C477522:S1PR2 protein, human
keywords: Inflammatory bowel disease (IBD); Intestinal mucosal barrier function; S1PR2; miR-126