LncRNA NEAT1 promotes extracellular matrix accumulation and epithelial-to-mesenchymal transition by targeting miR-27b-3p and ZEB1 in diabetic nephropathy

被引:74
作者
Wang, Xiaowei [1 ]
Xu, Yong [2 ]
Zhu, Ying-Chun [3 ]
Wang, Ya-Kun [3 ]
Li, Ji [3 ]
Li, Xiao-Ying [3 ]
Ji, Tingting [3 ]
Bai, Shou-Jun [3 ]
机构
[1] Fudan Univ, Zhongshan Hosp, Dept Endocrinol, Qingpu Branch, Shanghai, Peoples R China
[2] Xuzhou Med Univ, Huaian Hosp, Dept Nephrol, Huaian, Peoples R China
[3] Fudan Univ, Zhongshan Hosp, Dept Nephrol, Qingpu Branch, 1158 Gongyuan East Rd, Shanghai 201700, Peoples R China
关键词
diabetic nephropathy; miR-27b-3p; NEAT1; ZEB1; LONG NONCODING RNAS; TGF-BETA; RENAL FIBROSIS; PROLIFERATION; TRANSCRIPTION; MICRORNAS; CELLS;
D O I
10.1002/jcp.27959
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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-1) 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.
引用
收藏
页码:12926 / 12933
页数:8
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