MicroRNA-377 is up-regulated and can lead to increased fibronectin production in diabetic nephropathy

FASEB J. 2008 Dec;22(12):4126-35. doi: 10.1096/fj.08-112326. Epub 2008 Aug 20.


Intrinsic glomerular cells in a diabetic milieu have transcriptional activation of genes that influence the development of diabetic nephropathy. The cellular repertoire of microRNAs can regulate translation of these expressed genes into proteins. Fibronectin is a key matrix protein accumulated in excess in diabetic nephropathy. Here, we exposed cultured human and mouse mesangial cells to high glucose and transforming growth factor-beta to simulate the diabetic milieu. In these conditions in vitro, as well as in mouse diabetic nephropathy models in vivo, microRNA-377 was consistently up-regulated relative to controls. Through a combination of computational and biological approaches, we identified relevant miR-377 target genes. Although fibronectin was induced by miR-377, it was not a direct target of miR-377. However, miR-377 led to reduced expressions of p21-activated kinase and superoxide dismutase, which enhanced fibronectin protein production. Thus, overexpression of miR-377 in diabetic nephropathy indirectly leads to increased fibronectin protein production; as such, miR-377 can have a critical role in the pathophysiology of this prevalent human disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Diabetic Nephropathies / metabolism*
  • Female
  • Fibronectins / biosynthesis*
  • Glomerular Mesangium / metabolism*
  • Humans
  • Mice
  • Mice, Inbred NOD
  • MicroRNAs / biosynthesis
  • MicroRNAs / physiology*
  • Phosphoprotein Phosphatases / biosynthesis
  • Protein Phosphatase 2C
  • Superoxide Dismutase / biosynthesis
  • Up-Regulation
  • p21-Activated Kinases / biosynthesis


  • Fibronectins
  • MIRN377 microRNA, human
  • MicroRNAs
  • Mirn377 microRNA, mouse
  • Superoxide Dismutase
  • superoxide dismutase 2
  • p21-Activated Kinases
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2C