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LncRNA NEAT1 promotes extracellular matrix accumulation and epithelial‐to‐mesenchymal transition by targeting miR‐27b‐3p and ZEB1 in diabetic nephropathy
Author(s) -
Wang Xiaowei,
Xu Yong,
Zhu YingChun,
Wang YaKun,
Li Ji,
Li XiaoYing,
Ji Tingting,
Bai ShouJun
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27959
Subject(s) - extracellular matrix , diabetic nephropathy , epithelial–mesenchymal transition , mesenchymal stem cell , microbiology and biotechnology , extracellular , cancer research , chemistry , downregulation and upregulation , diabetes mellitus , biology , endocrinology , biochemistry , gene
Diabetic nephropathy (DN) is a kind of microvascular complications of diabetes. Long noncoding RNAs (lnRNAs) can participate in the development of various diseases, including DN. However, the function of lncRNA NEAT1 is unclear. In our present study, we reported that NEAT1 was significantly increased in streptozotocin‐induced DN rat models and high‐glucose‐induced mice mesangial cells. We observed that knockdown of NEAT1 greatly inhibited renal injury of DN rats. Meanwhile, downregulation of NEAT1‐modulated extracellular matrix (ECM) proteins (ASK1, fibronectin, and TGF‐β1) expression and epithelial–mesenchymal transition (EMT) proteins (E‐cadherin and N‐cadherin) in vitro. Previously, miR‐27b‐3p has been reported to be involved in diabetes. Here, miR‐27b‐3p was decreased in DN rats and high‐glucose‐induced mice mesangial cells. The direct correlation between NEAT1 and miR‐27b‐3p was validated using the dual‐luciferase reporter assay and RNA immunoprecipitation experiments. In addition, zinc finger E‐box binding homeobox 1 (ZEB1), which has been identified in the process of EMT clearly contributes to EMT progression. ZEB1 was predicted as a target of miR‐27b‐3p and overexpression of miR‐27b‐3p dramatically repressed ZEB1 expression. Therefore, our data implied the potential role of NEAT1 in the fibrogenesis and EMT in DN via targeting miR‐27b‐3p and ZEB1.