Abstract: PUB394
PGC-1α Mediates Hypothermic Renal Protection in a Mouse Model of Ischemia-Reperfusion-Induced Renal Fibrosis
Session Information
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Park, Heewon, Chungnam National University Sejong Hospital, Sejong, Korea (the Republic of)
- Choi, Dae Eun, Chungnam National University Hospital, Daejeon, Korea (the Republic of)
- Kim, Hae Ri, Chungnam National University Sejong Hospital, Sejong, Korea (the Republic of)
- Park, Kyungho, Chungnam National University Hospital, Daejeon, Korea (the Republic of)
- Lee, Eu Jin, Chungnam National University Hospital, Daejeon, Korea (the Republic of)
- Ham, Youngrok, Chungnam National University School of Medicine, Daejeon, Korea (the Republic of)
Background
Hypothermia has been widely studied for its protective effects against acute kidney injury resulting from ischemia-reperfusion injury (IRI). However, its role in attenuating subsequent renal fibrosis remains insufficiently understood. This study aimed to evaluate the renoprotective effects of hypothermia in an IRI-induced fibrosis model and to explore the role of PGC-1α in mediating these effects.
Methods
A murine model of renal IRI was established in male C57BL/6 mice, which were assigned to either normothermic (37°C) or hypothermic (32°C) IRI groups. Sham-operated mice served as controls. Kidney tissues were collected on days 1, 3, and 7 post-IRI. Renal injury and fibrosis were assessed through histological evaluation and molecular analyses. In vitro studies were performed using HK-2 cells treated with TGF-β, with or without cold preconditioning and PGC-1α knockdown via siRNA.
Results
Mice subjected to hypothermic IRI exhibited significantly improved renal function, as indicated by lower serum creatinine and BUN levels, along with improved histological injury scores, compared to the normothermic IRI group. Hypothermia downregulated profibrotic markers TGF-β and α-SMA, while upregulating PGC-1α expression in renal tissue. In HK-2 cells, cold preconditioning enhanced PGC-1α levels and attenuated TGF-β-induced α-SMA and collagen IV expression. The antifibrotic effects of hypothermia were abolished by siRNA-mediated knockdown of PGC-1α, confirming its essential role.
Conclusion
Hypothermia alleviates renal injury and fibrosis following ischemia-reperfusion by modulating PGC-1α. These findings suggest that PGC-1α is a key molecular mediator in hypothermia-induced renoprotection and a potential therapeutic target for preventing fibrosis in chronic kidney disease following acute injury.