MicroRNA-29b inhibits diabetic nephropathy in db/db mice

Mol Ther. 2014 Apr;22(4):842-53. doi: 10.1038/mt.2013.235. Epub 2013 Dec 6.


Inflammation and its consequent fibrosis are two main features of diabetic nephropathy (DN), but target therapy on these processes for DN remains yet ineffective. We report here that miR-29b is a novel therapeutic agent capable of inhibiting progressive renal inflammation and fibrosis in type 2 diabetes in db/db mice. Under diabetic conditions, miR-29b was largely downregulated in response to advanced glycation end (AGE) product, which was associated with upregulation of collagen matrix in mesangial cells via the transforming growth factor-β (TGF-β)/Smad3-dependent mechanism. These pathological changes were reversed by overexpressing miR-29b, but enhanced by knocking-down miR-29b. Similarly, loss of renal miR-29b was associated with progressive diabetic kidney injury, including microalbuminuria, renal fibrosis, and inflammation. Restored renal miR-29b by the ultrasound-based gene therapy was capable of attenuating diabetic kidney disease. Further studies revealed that inhibition of Sp1 expression, TGF-β/Smad3-dependent renal fibrosis, NF-κB-driven renal inflammation, and T-bet/Th1-mediated immune response may be mechanisms associated with miR-29b treatment in db/db mice. In conclusion, miR-29b may play a protective role in diabetic kidney disease and may have therapeutic potential for diabetic kidney complication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / therapy*
  • Diabetic Nephropathies / genetics*
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / therapy
  • Disease Models, Animal
  • Fibrosis / genetics
  • Fibrosis / therapy
  • Genetic Therapy
  • Humans
  • Inflammation / genetics
  • Inflammation / pathology
  • Inflammation / therapy*
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / therapeutic use*
  • Signal Transduction
  • Smad3 Protein / genetics
  • Transforming Growth Factor beta / genetics


  • MIRN29 microRNA, mouse
  • MicroRNAs
  • Smad3 Protein
  • Smad3 protein, mouse
  • Transforming Growth Factor beta