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 language | English (US) |
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Pages (from-to) | 4126-4135 |
Number of pages | 10 |
Journal | FASEB Journal |
Volume | 22 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2008 |
Externally published | Yes |
Keywords
- Diabetes
- Extracellular matrix
- Glomerulus
- microRNA
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics