کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2816916 | 1159957 | 2013 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Aldosterone stimulates fibronectin synthesis in renal fibroblasts through mineralocorticoid receptor-dependent and independent mechanisms Aldosterone stimulates fibronectin synthesis in renal fibroblasts through mineralocorticoid receptor-dependent and independent mechanisms](/preview/png/2816916.png)
In addition to its role in regulation of salt transport in the kidney, the mineralocorticoid hormone aldosterone plays an independent role as a mediator of kidney injury and progression of chronic kidney disease. Studies in both animal models and patients have shown that aldosterone enhances the accumulation of extracellular matrix and progression of fibrosis in the kidney. However, the cellular mechanisms that lead to aldosterone-dependent fibrogenesis are poorly understood. In this study we find that aldosterone stimulates fibronectin synthesis through mineralocorticoid receptor (MCR) dependent activation of the c-Jun NH2-terminal protein kinase (JNK) and subsequent phosphorylation of the AP1 transcription factor c-jun, which forms a nuclear complex with the mineralocorticoid receptor in a kidney fibroblast cell line (NRK 49f). Furthermore, MCR-independent phosphorylation of Src family kinase induces IgF1 receptor phosphorylation, which leads to stimulation of the extracellular signal-regulated kinase (ERK1/2) to enhanced fibronectin synthesis. We further find that the IgF1-R-dependent signaling pathway activates fibronectin expression faster than the MCR-dependent pathway. We propose that the mechanisms described in this study are important to aldosterone-dependent progression of interstitial fibrosis in the kidney. Due to the duality of aldosterone-dependent activation of fibronectin synthesis in kidney fibroblasts, MCR-specific inhibitors may not entirely prevent the progression of fibrosis by aldosterone in the kidney.
Journal: Gene - Volume 531, Issue 1, 15 November 2013, Pages 23–30