Hypothermia Mitigates Renal Fibrosis Through the Upregulation of PGC-1α After Ischemia–Reperfusion Injury
<b>Background:</b> Hypothermia has been previously reported to ameliorate acute renal injury induced by ischemia–reperfusion injury (IRI). However, its protective effects against subsequent renal fibrosis remain unclear. <b>Objectives</b>: The aim of this study was to determi...
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2025-05-01
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| author | Dabi Kim Suyeon Han Hyunsu Choi Yoon-Kyung Chang Dae Eun Choi |
| author_facet | Dabi Kim Suyeon Han Hyunsu Choi Yoon-Kyung Chang Dae Eun Choi |
| author_sort | Dabi Kim |
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| description | <b>Background:</b> Hypothermia has been previously reported to ameliorate acute renal injury induced by ischemia–reperfusion injury (IRI). However, its protective effects against subsequent renal fibrosis remain unclear. <b>Objectives</b>: The aim of this study was to determine whether hypothermia provides protection against renal ischemia–reperfusion injury (IRI), and to elucidate the molecular mechanisms involved. <b>Methods</b>: We used a model of renal fibrosis after ischemia–reperfusion injury in mice. C57BL/6 mice were divided into the following groups: control mice and ischemia–reperfusion injury mice (at 37 °C and at 32 °C). Their kidneys were harvested on day 1, day 3, and day 7 after IRI. The molecular mechanisms were evaluated. <b>Results</b>: The blood urea nitrogen (BUN) levels, serum creatinine (s-Cr) levels, and the histologic renal injury scores were significantly lower in the 32 °C IRI group than in the 37 °C ischemia–reperfusion injury group. In the hypothermic IR group, TGF-β and α-SMA were significantly decreased, while the PGC-1α level was significantly increased. Cold preparation increased the PGC-1α levels in HK2 cells. In TGF-β-treated HK2 cells, cold preparation decreased α-SMA and collagen IV levels. In addition, siPGC-1α in HK2 cells increased α-SMA and collagen IV, despite cold preparation. <b>Conclusions</b>: Hypothermia attenuates renal function deterioration and renal fibrosis in renal IRI mice kidneys. PGC-1α may play a role in hypothermic protection in renal fibrosis after IRI. |
| format | Article |
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| spelling | doaj-art-8372bf5e4174405d99d905f4f7859f4e2025-08-20T02:24:26ZengMDPI AGBiomedicines2227-90592025-05-01136133710.3390/biomedicines13061337Hypothermia Mitigates Renal Fibrosis Through the Upregulation of PGC-1α After Ischemia–Reperfusion InjuryDabi Kim0Suyeon Han1Hyunsu Choi2Yoon-Kyung Chang3Dae Eun Choi4Department of Medical Science, Medical School, Chungnam National University, Daejeon 35015, Republic of KoreaDepartment of Nephrology, Daejeon Saint Mary’s Hospital, Catholic University of Korea, Daejeon 34943, Republic of KoreaClinical Research Institute, Daejeon Saint Mary’s Hospital, Catholic University of Korea, Daejeon 34943, Republic of KoreaDepartment of Nephrology, Daejeon Saint Mary’s Hospital, Catholic University of Korea, Daejeon 34943, Republic of KoreaDepartment of Medical Science, Medical School, Chungnam National University, Daejeon 35015, Republic of Korea<b>Background:</b> Hypothermia has been previously reported to ameliorate acute renal injury induced by ischemia–reperfusion injury (IRI). However, its protective effects against subsequent renal fibrosis remain unclear. <b>Objectives</b>: The aim of this study was to determine whether hypothermia provides protection against renal ischemia–reperfusion injury (IRI), and to elucidate the molecular mechanisms involved. <b>Methods</b>: We used a model of renal fibrosis after ischemia–reperfusion injury in mice. C57BL/6 mice were divided into the following groups: control mice and ischemia–reperfusion injury mice (at 37 °C and at 32 °C). Their kidneys were harvested on day 1, day 3, and day 7 after IRI. The molecular mechanisms were evaluated. <b>Results</b>: The blood urea nitrogen (BUN) levels, serum creatinine (s-Cr) levels, and the histologic renal injury scores were significantly lower in the 32 °C IRI group than in the 37 °C ischemia–reperfusion injury group. In the hypothermic IR group, TGF-β and α-SMA were significantly decreased, while the PGC-1α level was significantly increased. Cold preparation increased the PGC-1α levels in HK2 cells. In TGF-β-treated HK2 cells, cold preparation decreased α-SMA and collagen IV levels. In addition, siPGC-1α in HK2 cells increased α-SMA and collagen IV, despite cold preparation. <b>Conclusions</b>: Hypothermia attenuates renal function deterioration and renal fibrosis in renal IRI mice kidneys. PGC-1α may play a role in hypothermic protection in renal fibrosis after IRI.https://www.mdpi.com/2227-9059/13/6/1337hypothermic protectionrenal fibrosisischemia–reperfusion injury |
| spellingShingle | Dabi Kim Suyeon Han Hyunsu Choi Yoon-Kyung Chang Dae Eun Choi Hypothermia Mitigates Renal Fibrosis Through the Upregulation of PGC-1α After Ischemia–Reperfusion Injury Biomedicines hypothermic protection renal fibrosis ischemia–reperfusion injury |
| title | Hypothermia Mitigates Renal Fibrosis Through the Upregulation of PGC-1α After Ischemia–Reperfusion Injury |
| title_full | Hypothermia Mitigates Renal Fibrosis Through the Upregulation of PGC-1α After Ischemia–Reperfusion Injury |
| title_fullStr | Hypothermia Mitigates Renal Fibrosis Through the Upregulation of PGC-1α After Ischemia–Reperfusion Injury |
| title_full_unstemmed | Hypothermia Mitigates Renal Fibrosis Through the Upregulation of PGC-1α After Ischemia–Reperfusion Injury |
| title_short | Hypothermia Mitigates Renal Fibrosis Through the Upregulation of PGC-1α After Ischemia–Reperfusion Injury |
| title_sort | hypothermia mitigates renal fibrosis through the upregulation of pgc 1α after ischemia reperfusion injury |
| topic | hypothermic protection renal fibrosis ischemia–reperfusion injury |
| url | https://www.mdpi.com/2227-9059/13/6/1337 |
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