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

Qiang Wang, Youli Wang, Andrew W. Minto, Jinhua Wang, Qun Shi, Xinmin Li, Richard J. Quigg

Research output: Contribution to journalArticle

297 Scopus citations

Abstract

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-β 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.

Original languageEnglish (US)
Pages (from-to)4126-4135
Number of pages10
JournalFASEB Journal
Volume22
Issue number12
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

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Keywords

  • Diabetes
  • Extracellular matrix
  • Glomerulus
  • microRNA

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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