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
Processing time: 110 Days and 8.6 Hours
Abstract
BACKGROUND

Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy (PHx). At present, there is a lack of recognized safe, effective, and stable drugs to promote liver regeneration. It has been reported that vagus nerve signaling is beneficial to liver regeneration, but the potential mechanism at play here is not fully understood.

AIM

To explore the effect and mechanism of hepatic vagus nerve in liver regeneration after PHx.

METHODS

A PHx plus hepatic vagotomy (Hv) mouse model was established. The effect of Hv on liver regeneration after PHx was determined by comparing the liver regeneration levels of the PHx-Hv group and the PHx-sham group mice. In order to further investigate the role of interleukin (IL)-22 in liver regeneration inhibition mediated by Hv, the levels of IL-22 in the PHx-Hv group and the PHx-sham group was measured. The degree of liver injury in the PHx-Hv group and the PHx-sham group mice was detected to determine the role of the hepatic vagus nerve in liver injury after PHx.

RESULTS

Compared to control-group mice, Hv mice showed severe liver injury and weakened liver regeneration after PHx. Further research found that Hv downregulates the production of IL-22 induced by PHx and blocks activation of the signal transducer and activator of transcription 3 (STAT3) pathway then reduces the expression of various mitogenic and anti-apoptotic proteins after PHx. Exogenous IL-22 reverses the inhibition of liver regeneration induced by Hv and alleviates liver injury, while treatment with IL-22 binding protein (an inhibitor of IL-22 signaling) reduce the concentration of IL-22 induced by PHx, inhibits the activation of the STAT3 signaling pathway in the liver after PHx, thereby hindering liver regeneration and aggravating liver injury in PHx-sham mice.

CONCLUSION

Hv attenuates liver regeneration after hepatectomy, and the mechanism may be related to the fact that Hv downregulates the production of IL-22, then blocks activation of the STAT3 pathway.

Keywords: Interleukin-22, Partial hepatectomy, Hepatic vagotomy, Liver regeneration, Signal transducer and activator of transcription 3, Interleukin-22 binding protein

Core Tip: In this study, we investigated the role and mechanism of the vagus nerve in liver regeneration using a partial hepatectomy (PHx) plus hepatic vagotomy (Hv) mouse model. We found that Hv attenuates liver regeneration after hepatectomy, the mechanism may be related to the fact that Hv downregulates the production of interleukin-22, then blocks activation of the signal transducer and activator of transcription 3 pathway after PHx. These results provide a theoretical basis for the development of drugs that promote liver regeneration with the vagus nerve as a new target.