title: Downregulation of miR-30c promotes renal fibrosis by target CTGF in diabetic nephropathy.
abstract: MicroRNAs (miRs) play important roles in initiation and progression of many pathologic processes. However, the role of miR-30c in diabetic nephropathy (DN) remains unclear. This study was to determine whether miR-30c was involved in the mechanism of renal fibrosis by inhibiting target CTGF expression in DN. In this study, In Situ Hybridization(ISH), RT-PCR, cell transfection, western blotting and laser confocal telescope were used, respectively. ISH showed that miR-30c, concentrated in cytoplasmic foci in the proximity of the nucleus, was mainly localized in glomerular and renal tubular epithelial cells within the cortex. RT-PCR showed that miR-30c expression was significantly decreased in DN (p<0.05), consistent with of the results of ISH. Luciferase reporter gene assays showed that CTGF was a validated target of miR-30c. Furthermore, miR-30c overexpression directly decreased CTGF mRNA and protein. Conversely, miR-30c inhibitor enhanced CTGF expression. Interestingly, miR-30c expression was negatively correlated with ACR (r=-0.870, P=0.003) and positively correlated with Ccr (r=0.8230, P=0.01), whereas it was uncorrelated with KW/BW, SBP, HbA1C, HOMR-IR and T-Cho (p>0.05). More importantly, miR-30c mimics significantly decreased col-IV, FN, GSI, GBM, GA, MRA/CLA and ACR (p<0.05) and, in contrast, slightly but significantly increased Ccr (p<0.05). In conclusion, our results suggested that loss of miR-30c may contribute to the pathogenesis of DN by inhibiting target CTGF expression; replenishing miR-30c may ameliorate renal structure and function by reducing renal fibrosis in DN.
authors.affiliation: Department of Endocrinology, Gansu Provincial People's hospital, 204 Donggang West Road, Lanzhou 730000, PR China; Gansu Key Laboratory of Endocrine and metabolism, 204 Donggang West Road, Lanzhou 730000, PR China. Electronic address: doctorwang@aliyun.com.
authors.forename: Jinyang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of gynecology and obstetrics, Gansu Provincial People's hospital, 204 Donggang West Road, Lanzhou 730000, PR China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Duan
authors.affiliation: Gansu Key Laboratory of Endocrine and metabolism, 204 Donggang West Road, Lanzhou 730000, PR China. Electronic address: 981459844@qq.com.
authors.forename: Tiankang
authors.initials: T
authors.lastname: Guo
authors.affiliation: Metabolic Disease Center, School of Traditional Chinese medical, Capital Medical University, and Beijing Key Laboratory of TCM Collateral Disease Theory Research, Beijing 100069, China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, Gansu Provincial People's hospital, 204 Donggang West Road, Lanzhou 730000, PR China; Gansu Key Laboratory of Endocrine and metabolism, 204 Donggang West Road, Lanzhou 730000, PR China.
authors.forename: Limin
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Endocrinology, Gansu Provincial People's hospital, 204 Donggang West Road, Lanzhou 730000, PR China; Gansu Key Laboratory of Endocrine and metabolism, 204 Donggang West Road, Lanzhou 730000, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Hospital, Tianjin 300070, China.
authors.forename: Shaocheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Beijing Tongren hospital, Capital Medical University, Beijing 100730, China.
authors.forename: Jinkui
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D055513:Connective Tissue Growth Factor / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism
chemical_list: C526318:CCN2 protein, mouse; D035683:MicroRNAs; C534715:Mirn30d microRNA, mouse; D055513:Connective Tissue Growth Factor
keywords: Connective tissue growth factor (CTGF); Diabetic nephropathy (DN); MicroRNAs (miRs); Renal fibrosis; Renal structure and function