Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2016; 22(6): 2081-2091
Published online Feb 14, 2016. doi: 10.3748/wjg.v22.i6.2081
Interleukin-22 contributes to liver regeneration in mice with concanavalin A-induced hepatitis after hepatectomy
Ya-Min Zhang, Zi-Rong Liu, Zi-Lin Cui, Chao Yang, Long Yang, Yang Li, Zhong-Yang Shen
Ya-Min Zhang, Zi-Lin Cui, Long Yang, Yang Li, Zhong-Yang Shen, Department of Hepatobiliary Surgery, First Central Hospital, Tianjin 300192, China
Zi-Rong Liu, Chao Yang, First Central Clinic of Tianjin Medical University, Tianjin 300192, China
Author contributions: Zhang YM and Liu ZR contributed equally to this work; Zhang YM, Liu ZR and Cui ZL designed the research; Zhang YM, Liu ZR, Yang C, Yang L and Li Y performed the research; Zhang YM, Liu ZR, Yang L and Shen ZY contributed new reagents and analytic tools; Zhang YM, Liu ZR, Yang C, Cui ZL and Li Y analyzed the data; Zhang YM and Liu ZR wrote the paper.
Supported by National Natural Science Foundation of China, No. 81370576; and Application Foundation and Advanced Technology Research Plan of Tianjin, China, No. 14JCYBJC24800.
Institutional review board statement: This work was approved by the Ethics Committee of Tianjin First Central Hospital.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Institute of Laboratory Animal Sciences, CAMS and PUMC (IACUC protocol number: SCXK[Jing]2014-0004).
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional unpublished data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Zi-Rong Liu, Postgraduate, First Central Clinic of Tianjin Medical University, No. 24 Fukang road, Nankai District, Tianjin 300192, China. liuzirong0730@163.com
Telephone: +86-22-23626848
Received: June 20, 2015
Peer-review started: June 21, 2015
First decision: July 10, 2015
Revised: July 21, 2015
Accepted: October 23, 2015
Article in press: October 26, 2015
Published online: February 14, 2016
Processing time: 217 Days and 17 Hours
Abstract

AIM: To investigate the therapeutic effects and mechanisms of interleukin (IL)-22 in liver regeneration in mice with concanavalin A (ConA)-induced liver injury following 70% hepatectomy.

METHODS: Mice were injected intravenously with ConA at 10 μg/g body weight 4 d before 70% hepatectomy to create a hepatitis model, and recombinant IL-22 was injected at 0.125 μg/g body weight 30 min prior to 70% hepatectomy to create a therapy model. Control animals received an intravenous injection of an identical volume of normal saline.

RESULTS: IL-22 treatment prior to 70% hepatectomy performed under general anesthesia resulted in reductions in the biochemical and histological evidence of liver injury, earlier proliferating cell nuclear antigen expression and accelerated recovery of liver mass. IL-22 pretreatment also significantly induced signal transducer and activator of transcription factor 3 (STAT3) activation and increased the expression of a variety of mitogenic proteins, such as Cyclin D1. Furthermore, alpha fetal protein mRNA expression was significantly elevated after IL-22 treatment.

CONCLUSION: In this study, we demonstrated that IL-22 is a survival factor for hepatocytes and prevents and repairs liver injury by enhancing pro-growth pathways via STAT3 activation. Treatment with IL-22 protein may represent a novel therapeutic strategy for preventing liver injury in patients with liver disease who have undergone hepatectomy.

Keywords: Interleukin-22; Concanavalin A; Partial hepatectomy; Liver regeneration

Core tip: Interleukin (IL)-22 appears to play a protective role in inflammation and has also been demonstrated to have proliferative effects in a hepatocyte cell line, however, it has rarely been reported that the protective and proliferative effects exist simultaneously. In this article, we investigated the therapeutic effects and mechanisms of IL-22 in liver regeneration in mice with concanavalin A-induced liver injury following 70% hepatectomy. IL-22 played protective and survival roles against liver injury in this model.