Open AccessBMP-7 Attenuates TGF-β1-Induced Fibronectin Secretion and Apoptosis of NRK-52E Cells by the Suppression of miRNA-21
Author(s) -
Yu Zhong,
Zai-chun Xu,
Han Wun-Lun,
Yuchen Zhu
Publication year - 2016
Publication title -
oncology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 57
eISSN - 1555-3906
pISSN - 0965-0407
DOI - 10.3727/096504016x14519157902645
Subject(s) - fibronectin , secretion , apoptosis , transforming growth factor , microbiology and biotechnology , fas ligand , gene knockdown , bone morphogenetic protein , microrna , transforming growth factor beta , biology , chemistry , programmed cell death , endocrinology , biochemistry , gene , extracellular matrix
Bone morphogenetic protein-7 (BMP-7) inhibited the pathogenesis of renal injury in response to a variety of stimuli. However, little is known about the molecular regulation and mechanism of endogenous BMP-7 and its renoprotective functions. This study examined the regulation of BMP-7 and its role in the fibronectin secretion and apoptosis of NRK-52E cells resulting from transforming growth factor-β1 (TGF-β1) in vitro. Results showed that TGF-β1 promoted factor-associated suicide (FAS), FAS ligand (FASL), fibronectin (FN), and miRNA-21 expression, while it downregulated phospho-Smad1 (pSmad1), pSmad5, and pSmad8 expressions in NRK-52E cells. In contrast, BMP-7 alleviated TGF-β1-induced cell apoptosis, inhibited TGF-β1-induced higher expression of miRNA-21 and FN, and enhanced TGF-β1-attenuated phosphorylation of Smad1, Smad5, and Smad8. Furthermore, a chemical inhibitor of miRNA-21 also negatively affected TGF-β1-induced apoptosis and FN secretion. On the other hand, overexpression of miRNA-21 counteracted the inhibitory effect of BMP-7 on TGF-β1-induced FN secretion and apoptosis. However, BMP-7 showed no effects on TGF-β1-induced FN secretion and apoptosis following knockdown of miRNA-21. Taken together, these findings demonstrated that BMP-7 might inhibit TGF-β1-induced FN secretion and apoptosis by the suppression of miRNA-21 in NRK-52E cells.