title: microRNA-125b contributes to high glucose-induced reactive oxygen species generation and apoptosis in HK-2 renal tubular epithelial cells by targeting angiotensin-converting enzyme 2.
abstract: Hyperglycemia induces apoptosis of renal tubular epithelial cells and contributes to tubular injury in diabetic nephropathy. Angiotensin-converting enzyme 2 (ACE2) is known to protect against diabetic kidney injury. However, the mechanism for the dysregulation of ACE2 expression in diabetic nephropathy is unclear.
  
  
  
  Bioinformatic analysis and luciferase reporter assay were done to identify ACE2-targeting microRNAs. Gain- and loss-of-function experiments were performed to determine the biological roles of the ACE2-targeting microRNAs in high glucose-induced damage to renal tubular epithelial cells.
  
  
  
  We identified microRNA-125b (miR-125b) as a negative regulator of ACE2. After high glucose treatment, HK-2 renal tubular epithelial cells showed an upregulation of miR-125b and reduction of ACE2 expression. Knockdown of miR-125b with anti-miR-125b inhibitors significantly prevented high glucose-induced downregulation of ACE2 in HK-2 cells. Moreover, depletion of miR-125b significantly blocked reactive oxygen species (ROS) formation and apoptosis in high glucose-exposed HK-2 cells. In contrast, ectopic expression of miR-125b accelerated ROS production and apoptotic response in HK-2 cells, which was coupled with induction of Bax and reduction of Bcl-2. Rescue experiments demonstrated that overexpression of ACE2 reversed the effects of miR-125b on ROS generation, apoptosis, and deregulation of Bcl-2 and Bax in HK-2 cells.
  
  
  
  Taken together, miR-125b mediates high glucose-induced ROS production and apoptosis in HK-2 renal tubular epithelial cells, largely through targeting ACE2. Accordingly, miR-125b represents a potential therapeutic target for the prevention of diabetic nephropathy.
authors: Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China. ghxding@gmail.com.
authors: Y-F
authors: YF
authors: Huang
authors: Y
authors: Y
authors: Zhang
authors: C-X
authors: CX
authors: Liu
authors: J
authors: J
authors: Huang
authors: G-H
authors: GH
authors: Ding
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D017209:Apoptosis; D004847:Epithelial Cells; D005947:Glucose; D006801:Humans; D007684:Kidney Tubules; D035683:MicroRNAs / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A; D017382:Reactive Oxygen Species
chemical_list: C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; D005947:Glucose