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Renalase Protects against Renal Fibrosis by Inhibiting the Activation of the ERK Signaling Pathways.
Int J Mol Sci. 2017 Apr 27; 18(5)IJ

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.

Authors+Show Affiliations

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. wyryyyy@163.com.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. wangliyan7731@sina.com.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. dazziling@163.com.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. yyzqd2007@126.com.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. liuwenhu2013@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28448446

Citation

Wu, Yiru, et al. "Renalase Protects Against Renal Fibrosis By Inhibiting the Activation of the ERK Signaling Pathways." International Journal of Molecular Sciences, vol. 18, no. 5, 2017.
Wu Y, Wang L, Deng D, et al. Renalase Protects against Renal Fibrosis by Inhibiting the Activation of the ERK Signaling Pathways. Int J Mol Sci. 2017;18(5).
Wu, Y., Wang, L., Deng, D., Zhang, Q., & Liu, W. (2017). Renalase Protects against Renal Fibrosis by Inhibiting the Activation of the ERK Signaling Pathways. International Journal of Molecular Sciences, 18(5). https://doi.org/10.3390/ijms18050855
Wu Y, et al. Renalase Protects Against Renal Fibrosis By Inhibiting the Activation of the ERK Signaling Pathways. Int J Mol Sci. 2017 Apr 27;18(5) PubMed PMID: 28448446.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renalase Protects against Renal Fibrosis by Inhibiting the Activation of the ERK Signaling Pathways. AU - Wu,Yiru, AU - Wang,Liyan, AU - Deng,Dai, AU - Zhang,Qidong, AU - Liu,Wenhu, Y1 - 2017/04/27/ PY - 2017/02/05/received PY - 2017/03/30/revised PY - 2017/04/04/accepted PY - 2017/4/28/entrez PY - 2017/4/28/pubmed PY - 2018/1/23/medline KW - ERK signaling pathway KW - chronic kidney disease KW - epithelial–mesenchymal transition KW - renal interstitial fibrosis KW - renalase JF - International journal of molecular sciences JO - Int J Mol Sci VL - 18 IS - 5 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/28448446/Renalase_Protects_against_Renal_Fibrosis_by_Inhibiting_the_Activation_of_the_ERK_Signaling_Pathways_ L2 - https://www.mdpi.com/resolver?pii=ijms18050855 DB - PRIME DP - Unbound Medicine ER -