title: Tongxinluo ameliorates renal structure and function by regulating miR-21-induced epithelial-to-mesenchymal transition in diabetic nephropathy.
abstract: Diabetic nephropathy (DN) is one of the most important diabetic microangiopathies. The epithelial-to-mesenchymal transition (EMT) plays an important role in DN. The physiological role of microRNA-21 (miR-21) was closely linked to EMT. However, it remained elusive whether tongxinluo (TXL) ameliorated renal structure and function by regulating miR-21-induced EMT in DN. This study aimed to determine the effect of TXL on miR-21-induced renal tubular EMT and to explore the relationship between miR-21 and TGF-β1/smads signals. Real-time RT-PCR, cell transfection, in situ hybridization (ISH), and laser confocal microscopy were used, respectively. Here, we revealed that TXL dose dependently lowered miR-21 expression in tissue, serum, and cells. Overexpression of miR-21 can enhance α-smooth muscle actin (SMA) expression and decrease E-cadherin expression by upregulating smad3/p-smad3 expression and downregulating smad7 expression. Interestingly, TXL also increased E-cadherin expression and decreased α-SMA expression by regulating miR-21 expression. More importantly, TXL decreased collagen IV, fibronectin, glomerular basement membrane, glomerular area, and the albumin/creatinine ratio, whereas it increased the creatinine clearance ratio. The results demonstrated that TXL ameliorated renal structure and function by regulating miR-21-induced EMT, which was one of the mechanisms to protect against DN, and that miR-21 may be one of the therapeutic targets for TXL in DN.
authors.affiliation: Metabolic Disease Center, School of Traditional Chinese Medicine, Capital Medical Univ. 10, Youanmenwai Xitoutiao, Fengtai District, Beijing, 100069, People's Republic of China. gaoyb111@hotmail.com.
authors.forename: Jin-yang
authors.initials: JY
authors.lastname: Wang
authors.forename: Yan-bin
authors.initials: YB
authors.lastname: Gao
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Da-wei
authors.initials: DW
authors.lastname: Zou
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Xu
authors.forename: Zhi-yao
authors.initials: ZY
authors.lastname: Zhu
authors.forename: Jiao-yang
authors.initials: JY
authors.lastname: Li
authors.forename: Sheng-nan
authors.initials: SN
authors.lastname: Zhou
authors.forename: Fang-qiang
authors.initials: FQ
authors.lastname: Cui
authors.forename: Xiang-jun
authors.initials: XJ
authors.lastname: Zeng
authors.forename: Jian-guo
authors.initials: JG
authors.lastname: Geng
authors.forename: Jin-kui
authors.initials: JK
authors.lastname: Yang
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*
chemical_list: D015820:Cadherins; D004365:Drugs, Chinese Herbal; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C513941:tongxinluo
keywords: diabetic nephropathy; epithelial-to-mesenchymal transition (EMT); microRNA; tongxinluo (TXL)