title: Expression of miR-106b-25 induced by salvianolic acid B inhibits epithelial-to-mesenchymal transition in HK-2 cells.
abstract: Epithelial-to-mesenchymal transition (EMT) is a highly conserved physiological program involved in renal fibrosis. Previous studies have shown that transforming growth factor (TGF)-β1 induces EMT in human kidney proximal tubular epithelial cells (HK-2 cells), whereas salvianolic acid B (Sal B) has a protective effect against EMT. The molecular pathogenesis of such processes is currently not well understood. In this study, a miRCURYTM LNA Array was used to screen HK-2 cells for expression changes of microRNAs (miRNAs) implicated in EMT. After validation by real-time PCR, all three members of the miR-106b-25 cluster (miR-106b, miR-93, and miR-25) were found to be markedly down-regulated during EMT in response to TGF-β1, whereas these miRNAs were up-regulated by Sal B treatment in a dose-dependent manner. Moreover, enhanced expression of miR-106b attenuated EMT by retaining the epithelial morphology of HK-2 cells, reducing the levels of α-smooth muscle actin (α-SMA), and increasing the levels of E-cadherin. To explore the molecular basis underlying the inhibitive effect of the miR-106b-25 cluster against EMT, bioinformatics analysis revealed that TGF-β type II receptor, a regulator of TGF-β signaling, might be a direct target of the miR-106b-25 cluster. In turn, low levels of TGF-β type II receptor in EMT of HK-2 cells were shown under the increase of miR-106b. In conclusion, our data suggest that the miR-106b-25 cluster may contribute to EMT in the kidney, and is involved in the protective effect of Sal B. Targeting of specific miRNAs may be a novel therapeutic approach to treat renal fibrosis.
authors.affiliation: Department of Nephrology, Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, PR China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Nephrology, Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, PR China.
authors.forename: Haizhen
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Department of Nephrology, Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, PR China.
authors.forename: Fengyan
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Nephrology, Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, PR China.
authors.forename: Jiayong
authors.initials: J
authors.lastname: Xie
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, School of Medicine, Nanjing University, Nanjing 210093, PR China. Electronic address: chenhuimei@nju.edu.cn.
authors.forename: Huimei
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, PR China. Electronic address: yg921@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Yao
mesh_terms: D001572:Benzofurans / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D035683:MicroRNAs / Q000819:agonists / Q000096:biosynthesis*; D053630:Depsides
chemical_list: D001572:Benzofurans; D035683:MicroRNAs; C542541:MIRN106 microRNA, human; C076944:salvianolic acid B; D053630:Depsides
keywords: Epithelial-to-mesenchymal transition; Salvianolic acid B; Salvianolic acid B (Pubchem CID: 11629084); Transforming growth factor-β1; miR-106b-25