Open Access

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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  • 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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August-2021
Volume 22 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Weng J, Wang X, Xu B and Li W: Augmenter of liver regeneration ameliorates ischemia-reperfusion injury in steatotic liver via inhibition of the TLR4/NF-κB pathway. Exp Ther Med 22: 863, 2021
APA
Weng, J., Wang, X., Xu, B., & Li, W. (2021). Augmenter of liver regeneration ameliorates ischemia-reperfusion injury in steatotic liver via inhibition of the TLR4/NF-κB pathway. Experimental and Therapeutic Medicine, 22, 863. https://doi.org/10.3892/etm.2021.10295
MLA
Weng, J., Wang, X., Xu, B., Li, W."Augmenter of liver regeneration ameliorates ischemia-reperfusion injury in steatotic liver via inhibition of the TLR4/NF-κB pathway". Experimental and Therapeutic Medicine 22.2 (2021): 863.
Chicago
Weng, J., Wang, X., Xu, B., Li, W."Augmenter of liver regeneration ameliorates ischemia-reperfusion injury in steatotic liver via inhibition of the TLR4/NF-κB pathway". Experimental and Therapeutic Medicine 22, no. 2 (2021): 863. https://doi.org/10.3892/etm.2021.10295