Abstract: SA-PO731
Hypothermic Protection Attenuates Renal Fibrosis After Renal Ischemia-Reperfusion
Session Information
- CKD: Mechanisms - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Kim, Da bi, Chungnam national university, Daejeon, Korea (the Republic of)
- Kim, Eunji, Chungnam national university, Daejeon, Korea (the Republic of)
- Jeong, Jin young, Chungnam national university, Daejeon, Korea (the Republic of)
- Kim, Jwajin, Chungnam National University, Daejeon, Korea (the Republic of)
- Chang, Yoon-Kyung, The Catholic University of Korea, Daejeon, Korea (the Republic of)
- Choi, Wonjung, Chungnam National University, Daejeon, Korea (the Republic of)
- Choi, Dae Eun, Chungnam National University, Daejeon, Korea (the Republic of)
- Na, Ki Ryang, Chungnam National University, Daejeon, Korea (the Republic of)
- Lee, Kang Wook, Chungnam National University, Daejeon, Korea (the Republic of)
Background
Hypothermia attenuates acute renal injury including tubular necrosis, detachment, and apoptosis after ischemia-reperfusion. However, it remains unknown whether hypothermia improve renal fibrosis. Although some reports showed cold ischemia activate TGF-bata signals, it is unclear that it induce the renal fibrosis. We evaluated the hypothermia reduced the renal fibrosis after renal ischemia-reperfusion injury.
Methods
C57Bl/6 mice were divided into the following groups: sham-operated (cold, 32C) vs normal temperature (37C); ischemia-reperfusion mice (32C vs 37C). Kidneys were harvested 20 minutes after induction of renal ischemia, 4hr, 24 hours, 72hr, and 168hr after ischemiareperfusion injury. Functional and molecular markers of kidney injury were evaluated. To explore the molecular mechanism involved the expression levels of renal HIF-1 and associated proteins were evaluated.
Results
The blood urea nitrogen and serum creatinine levels and the histologic renal injury scores were significantly lower in 32C ischemia-reperfusion than 37C ischemia-reperfusion kidneys (all P values < .05) at 24hr and 72hr after IR. Microscopic evaluation showed that renal fibrosis were significantly decrased in the kidneys of 32C compared to 37C ischemia-reperfusion mice at 4hr and 24hr after IR. The expression levels of Bax and caspase-3 and the extent of TUNEL and 8-OHdG cell positivity decreased, whereas the renal Bcl-2 level increased, in 32C ischemia-reperfusion compared to 37C ischemia-reperfusion mice. ERK and HIF1 phosphorylation was significantly increased in the kidneys of 32C compared to 37C ischemia-reperfusion mice at 4hr and 24hr after IR. However, TGF beta, SOX9, fibronectin, and collagen IV were significantly decrased in the kidneys of 32C compared to 37C ischemia-reperfusion mice at 4hr and 24hr after IR.
Conclusion
Hypothermic Protection increased the HIF1 and ERK phosphorylation. however it decreased the SOX9 and TGF beta signals. Hypothemia reduced the renal fibrosis after IR renal injury.
Funding
- Government Support - Non-U.S.