Abstract: SA-PO0243
Autophagy-Associated FIP200 Protects Renal Tubules Against Apoptosis After Renal Ischemia-Reperfusion Injury
Session Information
- AKI: Mechanisms - Cell Signaling
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Li, Guoli, Department of Nephrology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Li, Yi, Department of Nephrology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
Background
Acute kidney injury (AKI) easily progresses to chronic kidney diseases and end-stage renal diseases. Renal ischemia-reperfusion injury (IRI) is an important cause of AKI. Apoptosis is one of the main mechanisms of hypoxia-induced renal tubular epithelial cell death. Autophagy regulates apoptosis and plays a key role in the development of renal IRI. FAK family-interacting protein of 200 kDa (FIP200) is a crucial component of the ULK-1-Atg13-FIP200 complex formed in mammalian cells upon autophagy induction. Our previous study found that FIP200 might regulate the nuclear translocation of HMGB1 via modifying its acetylation caused by infection. However, the precise mechanisms of FIP200 underlying HMGB1 in renal IRI-mediated AKI remain elusive.
Methods
An in vitro hypoxia/reoxygenation (H/R) model was established in HK2 cells using the Billups hypoxic modular system across multiple timepoints. Animal experiments were approved by the Ethics Committee of Sichuan Provincial People's Hospital (No. L201735). Wild-type mice underwent renal pedicle clamping at varying durations to determine the optimal IRI timepoint. FIP200 conditional knockout mice (FKO: FIP200loxp-/loxp--Ggt cre/) and wild-type controls were then assigned to renal IRI or sham operation groups.
Results
In this study, we found that the expression of the autophagy-related protein FIP200 was up-regulated in vivo and in vitro after renal IRI or hypoxia/reoxygenation (H/R). Mice with conditional FIP200 knockout in renal tubules (FIP200loxp-/loxp--Ggt cre/mice) showed severe renal tissue damage after IRI. Additionally, overexpression and knockdown of FIP200 in HK2 cells revealed its protective effects on H/R injury of renal tubular epithelial cells. Further, we confirmed that FIP200 could interact with HMGB1 by immunoprecipitation assays and biolayer interferometry. Hence, we speculate that FIP200 could induce autophagy by regulating the competitive binding of HMGB1 and autophagy-related factors.
Conclusion
Our data indicate that FIP200 has an important role in preventing renal tubular cell damage and death following renal IRI, and might be a novel potential target for prevention and treatment of AKI caused by IRI.
Funding
- Government Support – Non-U.S.