title: BMP-7 Attenuates TGF-β1-Induced Fibronectin Secretion and Apoptosis of NRK-52E Cells by the Suppression of miRNA-21.
abstract: 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.
authors.affiliation: Department of Nephrology, Tongde Hospital of Zhejiang Province, Hangzhou, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Yu
authors.forename: Xu
authors.initials: X
authors.lastname: Zai-Chun
authors.forename: Han
authors.initials: H
authors.lastname: Wun-Lun
authors.forename: Zhu
authors.initials: Z
authors.lastname: Yun-Yun
mesh_terms: D000818:Animals; D017209:Apoptosis; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology / Q000502:physiology*; D002460:Cell Line; D005353:Fibronectins / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
chemical_list: C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D005353:Fibronectins; D035683:MicroRNAs; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; C546082:mirn21 microRNA, rat