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Int. J. Mol. Sci. 2017, 18(5), 855; doi:10.3390/ijms18050855

Renalase Protects against Renal Fibrosis by Inhibiting the Activation of the ERK Signaling Pathways

Department of Nephrology, Affiliated Beijing Friendship Hospital, Faculty of Kidney Diseases, Capital Medical University, No. 95 Yong An Road, Xi Cheng District, Beijing 100050, China
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Author to whom correspondence should be addressed.
Academic Editor: Gregor Drummen
Received: 5 February 2017 / Revised: 30 March 2017 / Accepted: 4 April 2017 / Published: 27 April 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

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-β1 (TGF-β1)-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 α-smooth muscle actin (α-SMA), fibronectin and collagen-I. In vitro, renalase inhibited TGF-β1-mediated upregulation of α-SMA and downregulation of E-cadherin. Increased levels of Phospho-extracellular regulated protein kinases (p-ERK1/2) in TGF-β1-stimulated cells were reversed by renalase cotreatment. When ERK1 was overexpressed, the inhibition of TGF-β1-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. View Full-Text
Keywords: renalase; chronic kidney disease; renal interstitial fibrosis; ERK signaling pathway; epithelial–mesenchymal transition renalase; chronic kidney disease; renal interstitial fibrosis; ERK signaling pathway; epithelial–mesenchymal transition
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Wu, Y.; Wang, L.; Deng, D.; Zhang, Q.; Liu, W. Renalase Protects against Renal Fibrosis by Inhibiting the Activation of the ERK Signaling Pathways. Int. J. Mol. Sci. 2017, 18, 855.

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