Exogenous Wnt1 Prevents Acute Kidney Injury and Its Subsequent Progression to Chronic Kidney Disease
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 over...
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2021.745816/full |
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| author | Xue Hong Yanni Zhou Dedong Wang Fuping Lyu Tianjun Guan Youhua Liu Youhua Liu Liangxiang Xiao |
| author_facet | Xue Hong Yanni Zhou Dedong Wang Fuping Lyu Tianjun Guan Youhua Liu Youhua Liu Liangxiang Xiao |
| author_sort | Xue Hong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T20:11:36Z |
| format | Article |
| id | doaj.art-d82feb5d362e4d9392ad5523ccb87d99 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-19T20:11:36Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-d82feb5d362e4d9392ad5523ccb87d992022-12-21T20:07:18ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-11-011210.3389/fphys.2021.745816745816Exogenous Wnt1 Prevents Acute Kidney Injury and Its Subsequent Progression to Chronic Kidney DiseaseXue Hong0Yanni Zhou1Dedong Wang2Fuping Lyu3Tianjun Guan4Youhua Liu5Youhua Liu6Liangxiang Xiao7State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Nephrology, Xiamen Hospital Affiliated to Beijing University of Chinese Medicine, Xiamen, ChinaDepartment of Nephrology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, ChinaDepartment of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, ChinaDepartment of Nephrology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, ChinaState Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesDepartment of Nephrology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, ChinaStudies 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.https://www.frontiersin.org/articles/10.3389/fphys.2021.745816/fullacute kidney injurychronic kidney diseaseWnt1β-cateninischemia-reperfusion injury |
| spellingShingle | Xue Hong Yanni Zhou Dedong Wang Fuping Lyu Tianjun Guan Youhua Liu Youhua Liu Liangxiang Xiao Exogenous Wnt1 Prevents Acute Kidney Injury and Its Subsequent Progression to Chronic Kidney Disease Frontiers in Physiology acute kidney injury chronic kidney disease Wnt1 β-catenin ischemia-reperfusion injury |
| title | Exogenous Wnt1 Prevents Acute Kidney Injury and Its Subsequent Progression to Chronic Kidney Disease |
| title_full | Exogenous Wnt1 Prevents Acute Kidney Injury and Its Subsequent Progression to Chronic Kidney Disease |
| title_fullStr | Exogenous Wnt1 Prevents Acute Kidney Injury and Its Subsequent Progression to Chronic Kidney Disease |
| title_full_unstemmed | Exogenous Wnt1 Prevents Acute Kidney Injury and Its Subsequent Progression to Chronic Kidney Disease |
| title_short | Exogenous Wnt1 Prevents Acute Kidney Injury and Its Subsequent Progression to Chronic Kidney Disease |
| title_sort | exogenous wnt1 prevents acute kidney injury and its subsequent progression to chronic kidney disease |
| topic | acute kidney injury chronic kidney disease Wnt1 β-catenin ischemia-reperfusion injury |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2021.745816/full |
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