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Long noncoding RNA NEAT1 accelerates the proliferation and fibrosis in diabetic nephropathy through activating Akt/mTOR signaling pathway
Author(s) -
Huang Shan,
Xu Yong,
Ge Xiaoxu,
Xu Bojin,
Peng Wenfang,
Jiang Xiaohong,
Shen Lisha,
Xia Lili
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.27770
Subject(s) - pi3k/akt/mtor pathway , gene knockdown , protein kinase b , downregulation and upregulation , microbiology and biotechnology , cancer research , cell growth , signal transduction , long non coding rna , biology , mesangial cell , chemistry , endocrinology , kidney , apoptosis , biochemistry , gene
Accumulating evidence has indicated the significant roles of long noncoding RNAs (lncRNAs) in the pathophysiology of diabetic nephropathy (DN). LncRNA nuclear enriched abundant transcript 1 (NEAT1) has been reported to exert a key role in the progression of several diseases including diabetes. However, the role of NEAT1 in the regulation of DP progression remains barely known. Therefore, our study aimed to investigate the role of NEAT1 in a streptozotocin‐induced diabetes model (DM) of rats and glucose‐induced mouse mesangial cell models. Currently, we found that NEAT1 was greatly upregulated in DM rats and glucose‐induced mice mesangial cells, in which a high activation of Akt/mTOR signaling was also observed. Then, it was shown that knockdown of NETA1 was able to reduce renal injury in DM rats obviously. In addition, cell counting kit‐8 assay and 5‐ethynyl‐2′‐deoxyuridine assay were carried out and we observed downregulation of NEAT1 significantly inhibited mesangial cell proliferation. Meanwhile, extracellular matrix proteins and messenger RNA (transforming growth factor β1, fibronectin, and collagen IV) expression was dramatically restrained by silencing of NEAT1 in the high glucose‐induced mesangial cells. Finally, knockdown of NEAT1 greatly reduced the expression of the phosphorylation of Akt and mammalian target of rapamycin (mTOR) in vitro. These findings revealed that the decrease of NEAT1 repressed the proliferation and fibrosis in DN via activating the Akt/mTOR signaling pathway, which might represent a novel pathological mechanism of DN progression.