Aldosterone induces collagen synthesis via activation of ER1/2 in renal proximal tubular epithelial cells
Guoshuang Xu, Wei Chen, Xiaowei Liu, Hanmin Wang, Hongbao Liu & Shurong Bai
Aldosterone play pivotal roles on renal fibrosis by inducing mesangial cells proliferation and stimulating collagen synthesis in renal fibroblasts. However, whether renal proximal tubules are involved in aldosterone-induced renal fibrosis is not yet identified. The aim of this study was to examine the potential role of aldosterone in collagen expression via activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in cultured human renal proximal tubular epithelial (HKC) cells. HKC cells were stimulated by aldosterone with different concentration and time, gene expression of collagen I, II, III and IV were measured by real-time polymerase chain reaction. Collagen III and IV, α-smooth muscle actin (α-SMA), and ERK1/2 were detected by Western blot analysis. Treatment with aldosterone increased ERK1/2 phosphorylation in a time-and dose-dependent manner. Aldosterone also increased α-SMA, collagen III and IV expression at 48 hours but had no effect on collagen I and II level. These effects could be prevented by pretreatment with ERK kinase inhibitor U0126, while could not be prevented by mineralocorticoid receptor antagonist spironolactone. The results suggest that aldosterone stimulates collagen synthesis may contribute to the progression of renal tubulointerstitial fibrosis. The process was at least partially mediated by ERK1/2 MAP kinase pathway, independent of mineralocorticoid receptor.