Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2022; 28(47): 6752-6768
Published online Dec 21, 2022. doi: 10.3748/wjg.v28.i47.6752
Interleukin-34 deficiency aggravates development of colitis and colitis-associated cancer in mice
Zhao-Xiu Liu, Wei-Jie Chen, Yang Wang, Bing-Qian Chen, Yi-Cun Liu, Tiao-Chun Cheng, Lei-Lei Luo, Lin Chen, Lin-Ling Ju, Yuan Liu, Ming Li, Nan Feng, Jian-Guo Shao, Zhao-Lian Bian
Zhao-Xiu Liu, Department of Gastroenterology and Hepatology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Wei-Jie Chen, Yang Wang, Bing-Qian Chen, Yi-Cun Liu, Tiao-Chun Cheng, Medical School, Nantong University, Nantong 226001, Jiangsu Province, China
Lei-Lei Luo, Jian-Guo Shao, Zhao-Lian Bian, Department of Gastroenterology and Hepatology, Nantong Third People’s Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226006, Jiangsu Province, China
Lin Chen, Lin-Ling Ju, Nantong Institute of Liver Diseases, Nantong Third People’s Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226006, Jiangsu Province, China
Yuan Liu, Department of Gastroenterology and Hepatology, The Sixth People’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China
Ming Li, Department of Traditional Chinese Medicine, Nantong Third People’s Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226006, Jiangsu Province, China
Nan Feng, Division of Emergency, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200120, China
Author contributions: Liu ZX performed the main part of the study; Chen WJ and Wang Y performed the main part of the study and wrote original draft; Liu YC, Cheng TC, Luo LL, Chen L, and Ju LL provided technical support and analyzed the data; Chen BQ, Liu Y, Li M, and Feng N contributed to part of the experiments; Shao JG designed the study and guided the manuscript writing; Bian ZL Conceived and designed the study; Liu ZX, Chen WJ, and Wang Y contributed equally to this work; all authors have read and approve the final manuscript.
Supported by the Science and Technology Bureau, No. MS22018007; Six Peak Talents in Jiangsu Province, No. YY-177; Project of Jiangsu Province Youth Medical Talent Development, No. QNRC2016400 and No. QNRC2016697; Project of Nantong Youth Medical Talent Development, No. 05; Youth Fund of the National Natural Science Foundation of China, No. 82000497; Youth Fund of the Natural Science Foundation of Jiangsu Province, No. BK20200965; and Scientific Research Fund of Nantong Health Commission, No. MB2020037.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Nantong Third People’s Hospital Affiliated to Nantong University and Affiliated Hospital of Nantong University.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Ethics Committee of Nantong University (No: S20151221-908).
Informed consent statement: All patients and healthy people signed an informed consent form.
Conflict-of-interest statement: All authors confirm that there are no conflicts of interest.
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: Zhao-Lian Bian, MD, PhD, Associate Chief Physician, Associate Professor, Doctor, Department of Gastroenterology and Hepatology, Nantong Third People’s Hospital, Affiliated Nantong Hospital 3 of Nantong University, No. 60 Middle Qingnian Road, Nantong 226006, Jiangsu Province, China. bianzhaolian1998@163.com
Received: August 29, 2022
Peer-review started: August 29, 2022
First decision: October 20, 2022
Revised: November 2, 2022
Accepted: November 22, 2022
Article in press: November 22, 2022
Published online: December 21, 2022
Processing time: 111 Days and 20.1 Hours
Abstract
BACKGROUND

Although expression of interleukin (IL)-34 is upregulated in active ulcerative colitis (UC), the molecular function and underlying mechanism are largely unclear.

AIM

To investigate the function of IL-34 in acute colitis, in a wound healing model and in colitis-associated cancer in IL-34-deficient mice.

METHODS

Colitis was induced by administration of dextran sodium sulfate (DSS), and carcinogenesis was induced by azoxymethane (AOM). Whether the impact of IL-34 on colitis was dependent on macrophages was validated by depletion of macrophages in a murine model. The association between IL-34 expression and epithelial proliferation was studied in patients with active UC.

RESULTS

IL-34 deficiency aggravated murine colitis in acute colitis and in wound healing phase. The effect of IL-34 on experimental colitis was not dependent on macrophage differentiation and polarization. IL-34-deficient mice developed more tumors than wild-type mice following administration of AOM and DSS. No significant difference was shown in degree of cellular differentiation in tumors between wild-type and IL-34-deficient mice. IL-34 was dramatically increased in the active UC patients as previously reported. More importantly, expression of IL-34 was positively correlated with epithelial cell proliferation in patients with UC.

CONCLUSION

IL-34 deficiency exacerbates colonic inflammation and accelerates colitis-associated carcinogenesis in mice. It might be served as a potential therapeutic target in UC.

Keywords: Interleukin-34; Ulcerative colitis; Mucosal healing; Colitis-associated cancer; Macrophage; Murine model

Core Tip: This study highlights the role of interleukin (IL)-34 in acute experimental colitis and wound healing phase in mice. We found that IL-34 did not drive inflammatory response and tissue destruction in physiological conditions, but protects the host from inflammatory injury and reduces the risk of colitis-associated cancer. IL-34 might serve as a potential therapeutic target for inducing mucosal healing in treatment of ulcerative colitis (UC) and reducing colitis-associated cancer in UC.