title: miR-21 is a key therapeutic target for renal injury in a mouse model of type 2 diabetes.
abstract: OBJECTIVE
  As microRNA-21 (miR-21) plays a pathological role in fibrosis, we hypothesised that it may be a therapeutic target for diabetic nephropathy.
  
  
  METHODS
  Abundance of miR-21 was examined in diabetic kidneys from db/db mice. The therapeutic potential of miR-21 in diabetic kidney injury was examined in db/db mice by an ultrasound-microbubble-mediated miR-21 small hairpin RNA transfer. In addition, the role and mechanisms of miR-21 in diabetic renal injury were examined in vitro under diabetic conditions in rat mesangial and tubular epithelial cell lines by overexpressing or downregulating miR-21.
  
  
  RESULTS
  In db/db mice, a mouse model of type 2 diabetes, renal miR-21 at age 20 weeks was increased twofold compared with db/m (+) mice at the same age, and this increase was associated with the development of microalbuminuria and renal fibrosis and inflammation. More importantly, gene transfer of miR-21 knockdown plasmids into the diabetic kidneys of db/db mice at age 10 weeks significantly ameliorated microalbuminuria and renal fibrosis and inflammation at age 20 weeks, revealing a therapeutic potential for diabetic nephropathy by targeting miR-21. Overexpression of miR-21 in kidney cells enhanced, but knockdown of miR-21 suppressed, high-glucose-induced production of fibrotic and inflammatory markers. Targeting Smad7 may be a mechanism by which miR-21 regulates renal injury because knockdown of renal miR-21 restored Smad7 levels and suppressed activation of the TGF-β and NF-κB signalling pathways.
  
  
  CONCLUSIONS
  Inhibition of miR-21 might be an effective therapy for diabetic nephropathy.
authors.affiliation: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, The New Territories, Hong Kong Special Administrative Region, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Zhong
authors.forename: A C K
authors.initials: AC
authors.lastname: Chung
authors.forename: H Y
authors.initials: HY
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Dong
authors.forename: X M
authors.initials: XM
authors.lastname: Meng
authors.forename: R
authors.initials: R
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.forename: F F
authors.initials: FF
authors.lastname: Hou
authors.forename: H Y
authors.initials: HY
authors.lastname: Lan
mesh_terms: D000818:Animals; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D016212:Transforming Growth Factor beta