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| HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway |
| Qing-Zhi Hu a , # , Zhen-Rui Cao b , # , Wei-Xiong Zheng c , Min-Jie Zhao d , Jun-Hua Gong d , Cong Chen a , Zhong-Jun Wu c , Rui Tao a , ∗ |
a Department of Hepatobiliary Surgery, Bishan Hospital of Chongqing Medical University, Chongqing 402760, China
b Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
c Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
d Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
∗Corresponding author.
E-mail address: taorui@vip.126.com (R. Tao).
# Contributed equally. |
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Abstract 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 downregu- lated 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.
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2024, Vol. 23 
