Renalase Prevents Renal Fibrosis by Inhibiting Endoplasmic Reticulum Stress and Down-Regulating GSK-3β/Snail Signaling

Wu, Yiru; Bai, Yu; Feng, Yiduo; Zhang, Qidong; Diao, Zongli; Liu, Wenhu

doi:10.7150/ijms.82192

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Int J Med Sci 2023; 20(5):669-681. doi:10.7150/ijms.82192 This issue Cite

Research Paper

Renalase Prevents Renal Fibrosis by Inhibiting Endoplasmic Reticulum Stress and Down-Regulating GSK-3β/Snail Signaling

Yiru Wu¹, Yu Bai¹, Yiduo Feng², Qidong Zhang¹, Zongli Diao¹, Wenhu Liu^1✉

1. Department of Nephrology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong An Road, Xi Cheng District, Beijing 100050, P. R. China.
2. Department of Nephrology, Beijing Tiantan Hospital, Capital Medical University, No.119 South Fourth Ring Road West, Fengtai District, Beijing,100070, P. R. China.

Citation:

Wu Y, Bai Y, Feng Y, Zhang Q, Diao Z, Liu W. Renalase Prevents Renal Fibrosis by Inhibiting Endoplasmic Reticulum Stress and Down-Regulating GSK-3β/Snail Signaling. Int J Med Sci 2023; 20(5):669-681. doi:10.7150/ijms.82192. https://www.medsci.org/v20p0669.htm

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Abstract

Background: Treating renal fibrosis is crucial to delaying chronic kidney disease. The glycogen synthase kinase-3β (GSK-3β)/Snail pathway regulates renal fibrosis and Renalase can ameliorate renal interstitial fibrosis. However, it is not clear whether GSK-3β/Snail signaling affects Renalase action. Here, we explored the role and mechanism of GSK-3β/Snail in the anti-fibrosis action of Renalase.

Materials and methods: We used mice with complete unilateral ureteral obstruction (UUO) and human proximal renal tubular epithelial (HK-2) cells with transforming growth factor-β1 (TGF-β1)-induced fibrosis to explore the role and regulatory mechanism of the GSK-3β/Snail pathway in the amelioration of renal fibrosis by Renalase.

Results: In UUO mice and TGF-β1-induced fibrotic HK-2 cells, the expression of p-GSK-3β-Tyr216/p-GSK-3β-Ser9, GSK-3β and Snail was significantly increased, and endoplasmic reticulum (ER) stress was activated. After Renalase supplementation, fibrosis was alleviated, ER stress was inhibited and p-GSK-3β-Tyr216/p-GSK-3β-Ser9, GSK-3β and Snail were significantly down-regulated. The amelioration of renal fibrosis by Renalase and its inhibitory effect on GSK-3β/Snail were reversed by an ER stress agonist. Furthermore, when an adeno-associated virus or plasmid was used to overexpress GSK-3β, the effect of Renalase on delaying renal fibrosis was counteracted, although ER stress markers did not change.

Conclusion: Renalase prevents renal fibrosis by down-regulating GSK-3β/Snail signaling through inhibition of ER stress. Exogenous Renalase may be an effective method of slowing or stopping chronic kidney disease progression.

Keywords: Renal fibrosis, Renalase, GSK-3β/Snail, Endoplasmic reticulum stress, Chronic kidney disease.

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APA

Wu, Y., Bai, Y., Feng, Y., Zhang, Q., Diao, Z., Liu, W. (2023). Renalase Prevents Renal Fibrosis by Inhibiting Endoplasmic Reticulum Stress and Down-Regulating GSK-3β/Snail Signaling. International Journal of Medical Sciences, 20(5), 669-681. https://doi.org/10.7150/ijms.82192.

ACS

Wu, Y.; Bai, Y.; Feng, Y.; Zhang, Q.; Diao, Z.; Liu, W. Renalase Prevents Renal Fibrosis by Inhibiting Endoplasmic Reticulum Stress and Down-Regulating GSK-3β/Snail Signaling. Int. J. Med. Sci. 2023, 20 (5), 669-681. DOI: 10.7150/ijms.82192.

NLM

CSE

Wu Y, Bai Y, Feng Y, Zhang Q, Diao Z, Liu W. 2023. Renalase Prevents Renal Fibrosis by Inhibiting Endoplasmic Reticulum Stress and Down-Regulating GSK-3β/Snail Signaling. Int J Med Sci. 20(5):669-681.

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