HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway.

Autor: Hu QZ; Department of Hepatobiliary Surgery, Bishan Hospital of Chongqing Medical University, Chongqing 402760, China., Cao ZR; Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China., Zheng WX; Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China., Zhao MJ; Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China., Gong JH; Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China., Chen C; Department of Hepatobiliary Surgery, Bishan Hospital of Chongqing Medical University, Chongqing 402760, China., Wu ZJ; Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China., Tao R; Department of Hepatobiliary Surgery, Bishan Hospital of Chongqing Medical University, Chongqing 402760, China. Electronic address: taorui@vip.126.com.
Jazyk: angličtina
Zdroj: Hepatobiliary & pancreatic diseases international : HBPD INT [Hepatobiliary Pancreat Dis Int] 2024 Aug; Vol. 23 (4), pp. 344-352. Date of Electronic Publication: 2023 Aug 22.
DOI: 10.1016/j.hbpd.2023.08.012
Abstrakt: 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-κB pathway in the liver (P < 0.05).
Conclusions: HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB 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.
Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
(Copyright © 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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