期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 18, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/ijms18050855
关键词
renalase; chronic kidney disease; renal interstitial fibrosis; ERK signaling pathway; epithelial-mesenchymal transition
资金
- National Natural Science Foundation of China
- Beijing Municipal Science and Technology Commission
Renal interstitial fibrosis is a common pathway for the progression of chronic kidney disease (CKD) to end-stage renal disease. Renalase, acting as a signaling molecule, has been reported to have cardiovascular and renal protective effects. However, its role in renal fibrosis remains unknown. In this study, we evaluated the therapeutic efficacy of renalase in rats with complete unilateral ureteral obstruction (UUO) and examined the inhibitory effects of renalase on transforming growth factor-beta 1 (TGF-beta 1)-induced epithelial-mesenchymal transition (EMT) in human proximal renal tubular epithelial (HK-2) cells. We found that in the UUO model, the expression of renalase was markedly downregulated and adenoviral-mediated expression of renalase significantly attenuated renal interstitial fibrosis, as evidenced by the maintenance of E-cadherin expression and suppressed expression of alpha-smooth muscle actin (alpha-SMA), fibronectin and collagen-I. In vitro, renalase inhibited TGF-beta 1-mediated upregulation of alpha-SMA and downregulation of E-cadherin. Increased levels of Phospho-extracellular regulated protein kinases (p-ERK1/2) in TGF-beta 1-stimulated cells were reversed by renalase cotreatment. When ERK1 was overexpressed, the inhibition of TGF-beta 1-induced EMT and fibrosis mediated by renalase was attenuated. Our study provides the first evidence that renalase can ameliorate renal interstitial fibrosis by suppression of tubular EMT through inhibition of the ERK pathway. These results suggest that renalase has potential renoprotective effects in renal interstitial fibrosis and may be an effective agent for slowing CKD progression.
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