HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF- κ B pathway
作者全名：Hu, Qing-Zhi; Cao, Zhen-Rui; Zheng, Wei-Xiong; Zhao, Min-Jie; Gong, Jun-Hua; Chen, Cong; Wu, Zhong-Jun; Tao, Rui
作者地址：[Hu, Qing-Zhi; Chen, Cong; Tao, Rui] Chongqing Med Univ, Bishan Hosp, Dept Hepatobiliary Surg, Chongqing 402760, Peoples R China; [Cao, Zhen-Rui] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiothorac Surg, Chongqing 400016, Peoples R China; [Zheng, Wei-Xiong; Wu, Zhong-Jun] Chongqing Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Chongqing 400016, Peoples R China; [Zhao, Min-Jie; Gong, Jun-Hua] Chongqing Med Univ, Affiliated Hosp 2, Dept Hepatobiliary Surg, Chongqing 400010, Peoples R China
通信作者：Tao, R (通讯作者)，Chongqing Med Univ, Bishan Hosp, Dept Hepatobiliary Surg, Chongqing 402760, Peoples R China.
来源：HEPATOBILIARY & PANCREATIC DISEASES INTERNATIONAL
ESI学科分类：CLINICAL MEDICINE
WOS号：WOS:001243221800002
JCR分区：Q2
影响因子：3.6
年份：2024
卷号：23
期号：4
开始页：344
结束页：352
文献类型：Article
关键词：Ischemia-reperfusion injury; Liver transplantation; Inflammation; HSP110; Heat shock proteins; NF-kappa B
摘要：Background: Ischemia-reperfusion injury (IRI) poses a significant challenge to liver transplantation (LT). The underlying mechanism primarily involves overactivation of the immune system. Heat shock protein 110 (HSP110) functions as a molecular chaperone that helps stabilize protein structures. Methods: An IRI model was established by performing LT on Sprague-Dawley rats, and HSP110 was silenced using siRNA. Hematoxylin-eosin staining, TUNEL, immunohistochemistry, ELISA and liver enzyme analysis were performed to assess IRI following LT. Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes. Results: Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT (P < 0.05). However, when rats were injected with siRNA-HSP110, IRI subsequent to LT was notably reduced (P < 0.05). Additionally, the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced (P < 0.05). Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-kappa B pathway in the liver (P < 0.05). Conclusions: HSP110 in the liver promotes IRI after LT in rats by activating the NF-kappa B pathway and inducing M1-type polarization of Kupffer cells. Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI. (c) 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.
基金机构：Natural Science Foundation of Chongqing [CSTB2022NSCQ-MSX0148]; National Natural Science Foundation of China [82170 6 6 6, 81873592]; Chongqing Research Program of Technological Innovation and Application Demonstration [cstc2021jscx-gksbX0060]
基金资助正文：This study was supported by grants from the Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0148) , the National Natural Science Foundation of China (82170 6 6 6 and 81873592) , and Chongqing Research Program of Technological Innovation and Application Demonstration (cstc2021jscx-gksbX0060) .
