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

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.