title: Regulation of podocyte lesions in diabetic nephropathy via miR-34a in the Notch signaling pathway.
abstract: BACKGROUND
  The activation of the Notch signaling pathway has been shown to play an important role in diabetic nephropathy (DN) development. Besides, Notch-1 is a target gene in miR-34a. However, the regulation of the podocyte lesions involved in DN by miR-34a has not been identified.
  
  
  METHODS
  This study utilized miR-34a mimics and small interfering RNA transfection to construct miR-34a overexpression and lower-expression model to investigate the effect of miR-34a on the regulation of the Notch signaling pathway and podocyte lesions in DN. Western blotting and real-time quantitative polymerase chain reaction were applied for the quantitative testing of mRNA and protein expression. Apoptosis of podocyte was detected by TUNEL staining.
  
  
  RESULTS
  In high-glucose (HG) conditions, miR-34a overexpression inhibited the expression of Notch 1, Jagged 1, NICD, Hes 1, and Hey 1 proteins. Further, cleaved caspase-3, Bax, and phosphorylation of p53 (p-p53) were reduced significantly. Therefore, miR-34a overexpression inhibited the Notch signaling pathway and podocyte lesions induced by HG. β-arrestin was slightly reduced in HG conditions. Meanwhile, miR-34a overexpression could remit the inhibition.
  
  
  CONCLUSIONS
  Results from this study provide evidence that miR-34a may offer a new approach for the treatment of diabetes.
authors.affiliation: Department of Endocrinology, Tianjin Hospital, Tianjin, P.R. China.
authors.forename: Xiangying
authors.initials: X
authors.lastname: Zhang
authors.forename: Shuping
authors.initials: S
authors.lastname: Song
authors.forename: Huixin
authors.initials: H
authors.lastname: Luo
mesh_terms: D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000473:pathology*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D050199:Podocytes / Q000473:pathology*; D051881:Receptor, Notch1 / Q000502:physiology; D015398:Signal Transduction
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1