Exogenous Wnt1 Prevents Acute Kidney Injury and Its Subsequent Progression to Chronic Kidney Disease

Frontiers in Physiology

Fuping Lyu¹  Yanni Zhou²  Liangxiang Xiao³  Tianjun Guan³  Dedong Wang³  Youhua Liu⁴  Xue Hong⁵ 

[1] Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China;Department of Nephrology, Xiamen Hospital Affiliated to Beijing University of Chinese Medicine, Xiamen, China;Department of Nephrology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China;Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States;State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China;

关键词: acute kidney injury;    chronic kidney disease;    Wnt1;    β-catenin;    ischemia-reperfusion injury;   

DOI  :  10.3389/fphys.2021.745816

来源: DOAJ

【 摘 要 】

Studies suggest that Wnt/β-catenin agonists are beneficial in the treatment of acute kidney injury (AKI); however, it remains elusive about its role in the prevention of AKI and its progression to chronic kidney disease (CKD). In this study, renal Wnt/β-catenin signaling was either activated by overexpression of exogenous Wnt1 or inhibited by administration with ICG-001, a small molecule inhibitor of β-catenin signaling, before mice were subjected to ischemia/reperfusion injury (IRI) to induce AKI and subsequent CKD. Our results showed that in vivo expression of exogenous Wnt1 before IR protected mice against AKI, and impeded the progression of AKI to CKD in mice, as evidenced by both blood biochemical and kidney histological analyses. In contrast, pre-treatment of ICG-001 before IR had no effect on renal Wnt/β-catenin signaling or the progression of AKI to CKD. Mechanistically, in vivo expression of exogenous Wnt1 before IR suppressed the expression of proapoptotic proteins in AKI mice, and reduced inflammatory responses in both AKI and CKD mice. Additionally, exogenous Wnt1 inhibited apoptosis of tubular cells induced by hypoxia-reoxygenation (H/R) treatment in vitro. To conclude, the present study provides evidences to support the preventive effect of Wnt/β-catenin activation on IR-related AKI and its subsequent progression to CKD.

【 授权许可】

Unknown