title: MicroRNA-21 regulates intestinal epithelial tight junction permeability.
abstract: Increased tight junction (TJ) barrier permeability, induced by tumour necrosis factor (TNF)-α, may lead to the defects in TJ barrier and subsequent development of inflammation. Recent evidence suggests that miR-21 is implicated in inflammatory diseases. However, the physiological role of miR-21 in intestinal permeability remains elusive. This study aimed to explore the role of miR-21 in intestinal epithelial tight junction permeability. The filter-grown Caco-2 monolayers model system was established to mimic intestinal barrier defect. The tight junction proteins were detected by immunofluorescence and western blot analysis. The expression of miR-21 was assessed by real-time polymerase chain reaction (PCR). We found that the expression of miR-21 was increased significantly in TNF-α induced intestinal TJ barrier defect model. miR-21 overexpression significantly enhanced while miR-21 knockdown significantly decreased intestinal permeability. In addition, miR-21 overexpression significantly increased while miR-21 knockdown significantly decreased the levels of interleukin-6, interleukin-8 and prostaglandin E2 in cell culture medium. Furthermore, miR-21 positively regulated Akt phosphorylation and negatively regulated Phosphatase and tensin homolog (PTEN) expression in Caco-2 cells. Our results suggest that miR-21 may regulate intestinal epithelial tight junction permeability through PTEN/PI3K/Akt signalling pathway. This promotes the feasibility of targeting miR-21 in the clinical to preserve the intestinal barrier.
authors.affiliation: Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, Jinshan, China.|Center of Emergency and Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Center of Emergency and Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, Jinshan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, Jinshan, China.|Departments of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Fan
mesh_terms: D015153:Blotting, Western; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D019108:Tight Junctions / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C508606:CXCL8 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: PI3K/Akt pathway; intestinal epithelial barrier; microRNA-21; tumour necrosis factor α