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

Article

关键词: SUPEROXIDE-DISMUTASE;    MESANGIAL CELLS;    ENDOTHELIAL-CELLS;    SIGNALING PATHWAY;    KIDNEY GLOMERULI;    RENAL INJURY;    ACTIVATION;    APOPTOSIS;    GLUCOSE;    MECHANISM;   

DOI  :  10.1096/fj.08-112326

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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