Abstract: PO0343
Tubular β-Catenin Ameliorates AKI by Restoring Mitochondrial Biogenesis
Session Information
- AKI: Mechanisms of Injury
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Li, Hongyu, University of Hong Kong, Hong Kong, Hong Kong
- Leung, Joseph C K, University of Hong Kong, Hong Kong, Hong Kong
- Chan, Loretta Y.Y., University of Hong Kong, Hong Kong, Hong Kong
- Li, Bin, University of Hong Kong, Hong Kong, Hong Kong
- Yiu, Wai Han, University of Hong Kong, Hong Kong, Hong Kong
- Tang, Sydney C.W., University of Hong Kong, Hong Kong, Hong Kong
Background
Renal tubular β-catenin signaling plays a protective role in acute kidney injury (AKI), but the underlying mechanisms remain unclear. Mitochondrial dysfunction is responsible for the pathogenesis of AKI. This study aims to investigate the role of β-catenin activation on mitochondrial biogenesis in tubular cells upon AKI and its underlying mechanism.
Methods
Loss- and gain-of-β-catenin function was established in mice with tubular cell-specific β-catenin stabilization (TubCat mice) and knockout (TubCatKO mice). Septic and aseptic AKI was induced by exposure to LPS or ischemia/reperfusion, respectively. Kidney injury was examined by NGAL immunohistochemical staining. Markers of mitochondrial biogenesis were determined by Western blot, real-time quantitative PCR and immunofluorescence staining. Signaling cascade was examined by Western blot.
Results
Compared to the controls, TubCat mice under septic and aseptic AKI had significantly alleviated kidney injury and enhanced mitochondrial biogenesis as indicated by (i) reduction of NGAL positive tubules; (ii) restoration of mitochondrial mass protein TOMM20 and mitochondrial biogenesis molecules PGC-1α and NRF1; (iii) increasing co-localization of PGC-1α and β-catenin in renal tubules and (iv) increasing FOXO3 signaling against septic and aseptic injury. Consistently, kidney injury, and mitochondrial dysfunction were aggravated in TubCatKO mice versus their control littermates.
Conclusion
In both septic and aseptic AKI, tubular β-catenin stabilization restores mitochondrial homeostasis through the FOXO3/PGC-1α signaling pathway.
Funding: General Research Fund (HKU 17119818), RGC Collaborative Research Fund (Ref: C7018-16G) and Hong Kong Society of Nephrology Research Grant (2019)