title: Overexpression of miR-34c inhibits high glucose-induced apoptosis in podocytes by targeting Notch signaling pathways.
abstract: Recent findings have shown that microRNAs play critical roles in the pathogenesis of diabetic nephropathy. miR-34c has been found to inhibit fibrosis and the epithelial-mesenchymal transition of kidney cells. However, the role of miR-34c in diabetic nephropathy has not been well studied. The current study was designed to investigate the role and potential underlying mechanism of miR-34c in regulating diabetic nephropathy. After treating podocytes with high glucose (HG) in vitro, we found that miR-34c was downregulated and that overexpression of miR-34c inhibited HG-induced podocyte apoptosis. The direct interaction between miR-34c and the 3'-untranslated region (UTR) of Notch1 and Jagged1 was validated by dual-luciferase reporter assay. Moreover, Notch1 and Jagged1 as putative targets of miR-34c were downregulated by miR-34c overexpression in HG-treated podocytes. Overexpression of miR-34c inhibited HG-induced Notch signaling pathway activation, as indicated by decreased expression of the Notch intracellular domain (NICD) and downstream genes including Hes1 and Hey1. Furthermore, miR-34c overexpression increased the expression of the anti-apoptotic gene Bcl-2, and decreased the expression of the pro-apoptotic protein Bax and cleaved Caspase-3. Additionally, the phosphorylation of p53 was also downregulated by miR-34c overexpression. Taken together, our findings suggest that miR-34c overexpression inhibits the Notch signaling pathway by targeting Notch1 and Jaggged1 in HG-treated podocytes, representing a novel and potential therapeutic target for the treatment of diabetic nephropathy.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, China.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Liu
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, China.
authors.forename: Lian-Yun
authors.initials: LY
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, China.
authors.forename: Tie-Chui
authors.initials: TC
authors.lastname: Zhu
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, China.
authors.forename: Rui-Fang
authors.initials: RF
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, China.
authors.forename: Shu-Long
authors.initials: SL
authors.lastname: Wang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Xinxiang Medical University Weihui 453100, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Bao
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002461:Cell Line, Transformed; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000633:toxicity*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051881:Receptor, Notch1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; C551848:MIRN34a microRNA, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins; D005947:Glucose
keywords: Diabetic nephropathy; Notch; cell apoptosis; microRNAs; podocytes