title: MicroRNA-130b improves renal tubulointerstitial fibrosis via repression of Snail-induced epithelial-mesenchymal transition in diabetic nephropathy.
abstract: MicroRNA-130b (miR-130b) downregulation has been identified in diabetes, but the role and mechanisms for miR-130b in mediating renal tubulointerstitial fibrosis in diabetic nephropathy (DN) remain unknown. We demonstrated that plasma miR-130b downregulation exhibited clinical and biological relevance as it was linked to increased serum creatinine, β2-microglobulin and proteinuria, increased Snail expression and tubulointerstitial fibrosis in renal biopsies of DN patients. MiR-130b inhibitor caused Snail upregulation and enhanced molecular features of epithelial-to-mesenchymal transition (EMT) in high glucose (30 mM) cultured NRK-52E cells. In contrast, miR-130b mimic downregulated Snail expression and increased epithelial hallmarks. Notably, Snail was identified as an miR-130b direct target and inversely correlated with E-CADHERIN expression. Furthermore, the miR-130b-dependent effects were due to Snail suppression that in turn deregulated E-CADHERIN, VIMENTIN, COLLAGEN IV and α-smooth muscle actin (α-SMA), key mediators of EMT. These effects were reproduced in streptozotocin-induced diabetic rats. Thus, we propose a novel role of the miR-130b-SNAIL axis in fostering EMT and progression toward increased tubulointerstitial fibrosis in DN. Detection of plasma miR-130b and its association with SNAIL can be extrapolated to quantifying the severity of renal tubulointerstitial fibrosis. Targeting miR-130b could be evaluated as a potential therapeutic approach for DN.
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou, 510515, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Geng
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou, 510515, China.
authors.forename: Zhanmei
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou, 510515, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Emergency, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000097:blood / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005355:Fibrosis / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007684:Kidney Tubules / Q000473:pathology*; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000378:metabolism*; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D000071250:Snail Family Transcription Factors; D001613:beta 2-Microglobulin; D003404:Creatinine
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