| Autor: |
Yu Zhang, Ziyi Wang, Chenyang Jia, Wenjie Yu, Xiangdong Li, Nan Xia, Huiling Nie, Likalamu Pascalia Wikana, Minhao Chen, Yong Ni, Sheng Han, Liyong Pu |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Cellular and Molecular Gastroenterology and Hepatology, Vol 17, Iss 1, Pp 149-169 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2352-345X |
| DOI: |
10.1016/j.jcmgh.2023.09.004 |
| Popis: |
Background & Aims: Hepatic ischemia-reperfusion injury is a significant complication of partial hepatic resection and liver transplantation, impacting the prognosis of patients undergoing liver surgery. The protein proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily synthesized by hepatocytes and has been implicated in myocardial ischemic diseases. However, the role of PCSK9 in hepatic ischemia-reperfusion injury remains unclear. This study aims to investigate the role and mechanism of PCSK9 in hepatic ischemia-reperfusion injury. Methods: We first examined the expression of PCSK9 in mouse warm ischemia-reperfusion models and AML12 cells subjected to hypoxia/reoxygenation. Subsequently, we explored the impact of PCSK9 on liver ischemia-reperfusion injury by assessing mitochondrial damage and the resulting inflammatory response. Results: Our findings reveal that PCSK9 is up-regulated in response to ischemia-reperfusion injury and exacerbates hepatic ischemia-reperfusion injury. Blocking PCSK9 can alleviate hepatocyte mitochondrial damage and the consequent inflammatory response mediated by ischemia-reperfusion. Mechanistically, this protective effect is dependent on mitophagy. Conclusions: Inhibiting PCSK9 in hepatocytes attenuates the inflammatory responses triggered by reactive oxygen species and mitochondrial DNA by promoting PINK1-Parkin–mediated mitophagy. This, in turn, ameliorates hepatic ischemia-reperfusion injury. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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