Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Dec 27, 2023; 15(12): 2866-2878
Published online Dec 27, 2023. doi: 10.4240/wjgs.v15.i12.2866
Hepatic vagotomy blunts liver regeneration after hepatectomy by downregulating the expression of interleukin-22
Heng Zhou, Ju-Ling Xu, San-Xiong Huang, Ying He, Xiao-Wei He, Sheng Lu, Bin Yao
Heng Zhou, Xiao-Wei He, Sheng Lu, Bin Yao, Department of Pharmacy, The First People’s Hospital of Huzhou, First Affiliated Hospital of Huzhou University, Huzhou 313000, Zhejiang Province, China
Ju-Ling Xu, Department of Medicine, Medical School of Huzhou University, Huzhou 313000, Zhejiang Province, China
San-Xiong Huang, Department of Hepatobiliary Surgery, The First People’s Hospital of Huzhou, Huzhou 313000, Zhejiang Province, China
Ying He, Zhejiang Provincial Key Laboratory of Media Biology and Pathogenic Control, Central Laboratory, First Affiliated Hospital of Huzhou University, Huzhou 313000, Zhejiang Province, China
Author contributions: Zhou H, Lu S, and Yao B designed this project; Zhou H, He Y, and He XW performed the experiments and contributed to the graph making; Xu JL and Huang SX were involved in the data analysis; the manuscript was written by Zhou H and finalized by Yao B.
Supported by the Natural Science Foundation of Zhejiang Province, No. LQ20H310002; the Scientific Technology Projects of Health and Medicine of Zhejiang Province, No. 2020KY308; and the Huzhou Science and Technology Fund, No. 2020GY39.
Institutional animal care and use committee statement: The operational procedures for the animal experiments were approved by the Medical Ethics Committee of the First Affiliated Hospital of Huzhou University (No. 2019015).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Bin Yao, BPharm, Chief Pharmacist, Department of Pharmacy, The First People’s Hospital of Huzhou, First Affiliated Hospital of Huzhou University, No. 158 Square Back Road, Wuxing District, Huzhou 313000, Zhejiang Province, China. 50228@zjhu.edu.cn
Received: September 8, 2023
Peer-review started: September 8, 2023
First decision: October 24, 2023
Revised: November 1, 2023
Accepted: November 17, 2023
Article in press: November 17, 2023
Published online: December 27, 2023
ARTICLE HIGHLIGHTS
Research background

There is a lack of recognized safe, effective, and stable drugs to promote liver regeneration at present, which greatly limits the progress of liver surgery. It has been reported that vagus nerve signaling is beneficial to liver regeneration, but the potential mechanism is not fully understood.

Research motivation

In previous studies, we found that blocking the hepatic vagus nerve would exacerbate liver injury caused by ischemia-reperfusion, indicating that the vagus nerve may play a protective role in liver injury. Unfortunately, we cannot determine the effect and mechanism of the vagus nerve in liver regeneration after hepatectomy so far.

Research objectives

Exploring the role and mechanism of hepatic vagus nerve in liver regeneration after partial hepatectomy (PHx).

Research methods

Establishing a PHx+ hepatic vagotomy (Hv) mice model. The effect of vagus on liver regeneration was determined by comparing the liver regeneration levels of the PHx-Hv group and the PHx-sham group mice. Quantikine enzyme-linked immunosorbent assay kit and molecular biology techniques (western blot, polymerase chain reaction, etc.) have been used to further investigate the potential mechanism of Hv on liver regeneration.

Research results

Hv mice showed severe liver injury and weakened liver regeneration after PHx compared to control-group mice. Hv downregulates the production of interleukin-22 (IL-22) induced by PHx, inhibiting the activation of the signal transducer and activator of transcription 3 (STAT3) pathway in the liver. Exogenous IL-22 supplementation reverse the inhibitory effect on liver regeneration induced by Hv, while IL-22 binding protein inhibits the activation of liver STAT3 signaling pathway after PHx, then hindering liver regeneration in PHx-sham mice.

Research conclusions

Hv inhibits the regeneration of residual liver after surgery by downregulating the production of IL-22 induced by PHx.

Research perspectives

We are currently planning to investigate whether drugs that protect the vagus nerve play a positive role in liver regeneration after PHx.