Augmenter of liver regeneration ameliorates ischemia-reperfusion injury in steatotic liver via inhibition of the TLR4/NF-κB pathway

Weng,Junhua; Wang,Xin; Xu,Baohong; Li,Wen

doi:10.3892/etm.2021.10295

Augmenter of liver regeneration ameliorates ischemia-reperfusion injury in steatotic liver via inhibition of the TLR4/NF-κB pathway

Authors:
- Junhua Weng
- Xin Wang
- Baohong Xu
- Wen Li
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Affiliations: Department of Gastroenterology, Beijing Lu He Hospital, Capital Medical University, Beijing 101149, P.R. China, Beijing Key Laboratory of Diabetes Research and Care Center for Endocrine Metabolism and Immune Diseases, Beijing Lu He Hospital, Capital Medical University, Beijing 101149, P.R. China, Department of Cell Biology and Municipal Laboratory of Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, P.R. China
Published online on: June 10, 2021 https://doi.org/10.3892/etm.2021.10295
Article Number: 863
Copyright: © Weng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocytes from donors with preexisting hepatic steatosis exhibited increased sensitivity to ischemia‑reperfusion injury (IRI) during liver transplantation. Augmenter of liver regeneration (ALR) protected the liver against IRI, but the mechanism was not clarified. Therefore, the hypothesis that ALR attenuated IRI in steatotic liver by inhibition of inflammation and downregulation of the Toll‑like receptor 4 (TLR4)/nuclear factor‑κB (NF‑κB) pathway was examined. C57BL/6 mice were subjected to a methionine‑choline‑deficient (MCD) diet to induce liver steatosis. Mice were transfected with ALR‑containing adenovirus 3 days prior to partial warm hepatic IRI. After 30 min of ischemia and 6 h of reperfusion injury, liver function, hepatic injury, the inflammatory response and TLR4/NF‑κB signaling pathway activation were assessed. ALR maintained liver function and alleviated hepatic injury as indicated by the decreased levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), preserved hepatic structure and reduced apoptosis. ALR also reduced the IRI‑induced inflammatory response by suppressing Kupffer cell activation, inhibiting neutrophil chemotaxis and reducing inflammatory cytokine production. Further investigation using reverse transcription‑quantitative PCR, western blotting and immunohistochemistry revealed that ALR reduced TLR4/NF‑κB signaling pathway activation, which led to a decreased synthesis of inflammatory cytokines. ALR functioned as a regulator of the IRI‑induced inflammatory response by suppressing the TLR4/NF‑κB pathway, which supports the use of ALR in therapeutic applications for fatty liver transplantation.

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