Tang RX, Xie XJ, Xiong Y, Li S, Luo C, Wang YG. C23 ameliorates carbon tetrachloride-induced liver fibrosis in mice. World J Hepatol 2024; 16(9): 1278-1288 [PMID: 39351519 DOI: 10.4254/wjh.v16.i9.1278]
Corresponding Author of This Article
Yi-Gang Wang, MD, Doctor, Department of Hepatopancreatobiliary Surgery, Panzhihua Municipal Central Hospital, No. 34 Yikang street, East District, Panzhihua 617000, Sichuan Province, China. wyg18096306896@163.com
Research Domain of This Article
Biochemistry & Molecular Biology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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/
World J Hepatol. Sep 27, 2024; 16(9): 1278-1288 Published online Sep 27, 2024. doi: 10.4254/wjh.v16.i9.1278
C23 ameliorates carbon tetrachloride-induced liver fibrosis in mice
Rong-Xing Tang, Xiao-Jun Xie, Yong Xiong, Su Li, Chen Luo, Yi-Gang Wang
Rong-Xing Tang, Yong Xiong, Su Li, Chen Luo, Yi-Gang Wang, Department of Hepatopancreatobiliary Surgery, Panzhihua Municipal Central Hospital, Panzhihua 617000, Sichuan Province, China
Xiao-Jun Xie, Department of Pathology, Panzhihua Maternal and Children Health Hospital, Panzhihua 617000, Sichuan Province, China
Co-first authors: Rong-Xing Tang and Xiao-Jun Xie.
Author contributions: Wang YG and Tang RX conducted conceptualization, Writing; Xie XJ conducted data curation; Xie XJ, Xiong Y and Li S conducted formal analysis; Xiong Y and Li S conducted investigation; Li S and Lou C conducted methodology. All authors have read and agreed to the published version of the manuscript.
Supported byThe Panzhihua Science and Technology Planning Project of China, No. 2023ZD-S-57.
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 General Hospital of Western Theater Command (protocol No. 2023EC004).
Conflict-of-interest statement: The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
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: Yi-Gang Wang, MD, Doctor, Department of Hepatopancreatobiliary Surgery, Panzhihua Municipal Central Hospital, No. 34 Yikang street, East District, Panzhihua 617000, Sichuan Province, China. wyg18096306896@163.com
Received: May 7, 2024 Revised: August 10, 2024 Accepted: August 21, 2024 Published online: September 27, 2024 Processing time: 138 Days and 18.3 Hours
Abstract
BACKGROUND
C23, an oligo-peptide derived from cold-inducible RNA-binding protein (CIRP), has been reported to inhibit tissue inflammation, apoptosis and fibrosis by binding to the CIRP receptor; however, there are few reports on its role in liver fibrosis and the underlying mechanism is unknown.
AIM
To explore whether C23 plays a significant role in carbon tetrachloride (CCl4)-induced liver fibrosis.
METHODS
CCl4 was injected for 6 weeks to induce liver fibrosis and C23 was used beginning in the second week. Masson and Sirius red staining were used to examine changes in fiber levels. Inflammatory factors in the liver were detected and changes in α-smooth muscle actin (α-SMA) and collagen I expression were detected via immunohistochemical staining to evaluate the activation of hematopoietic stellate cells (HSCs). Western blotting was used to detect the activation status of the transforming growth factor-beta (TGF-β)/Smad3 axis after C23 treatment.
RESULTS
CCl4 successfully induced liver fibrosis in mice, while tumor necrosis factor-alpha (TNF-α), IL (interleukin)-1β, and IL-6 levels increased significantly and the IL-10 level decreased significantly. Interestingly, C23 inhibited this process. On the other hand, C23 significantly inhibited the activation of HSCs induced by CCl4, which inhibited the expression of α-SMA and the synthesis of collagen I. In terms of mechanism, C23 can block Smad3 phosphorylation significantly and inhibits TGF-β/Smad3 pathway activation, thereby improving liver injury caused by CCl4.
CONCLUSION
C23 may block TGF-β/Smad3 axis activation, inhibit the expression of inflammatory factors, and inhibit the activation of HSCs induced by CCl4, alleviating liver fibrosis.
Core Tip: C23, an oligo-peptide derived from cold-inducible RNA-binding protein inhibits the activation of hepatic stellate cells induced with carbon tetrachloride and the expression of collagen I and α-smooth muscle actin. C23 inhibits the expression of liver inflammatory factors and downregulates transforming growth factor-beta/Smad3 pathway activation, thereby alleviating liver fibrosis.
