Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2025; 31(31): 109605
Published online Aug 21, 2025. doi: 10.3748/wjg.v31.i31.109605
TSC22D1 promotes liver sinusoidal endothelial cell dysfunction and induces macrophage M1 polarization in non-alcoholic fatty liver disease
Wei Ding, Xin-Qi Xu, Ling-Lin Wu, Qun Wang, Yi-Qin Wang, Wei-Wei Chen, Yu-Lin Tan, Yi-Bo Wang, Hua-Ji Jiang, Jun Dong, Yong-Min Yan, Xue-Zhong Xu
Wei Ding, Xin-Qi Xu, Qun Wang, Yi-Qin Wang, Wei-Wei Chen, Yu-Lin Tan, Yi-Bo Wang, Hua-Ji Jiang, Jun Dong, Xue-Zhong Xu, Department of General Surgery, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213162, Jiangsu Province, China
Wei Ding, Yu-Lin Tan, Department of General Surgery, The Wujin Clinical College of Xuzhou Medical University, Changzhou 213162, Jiangsu Province, China
Wei Ding, Department of General Surgery, Wujin Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou 213162, Jiangsu Province, China
Ling-Lin Wu, Department of Obstetrics and Gynecology, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213162, Jiangsu Province, China
Yong-Min Yan, Department of Laboratory, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213162, Jiangsu Province, China
Co-corresponding authors: Yong-Min Yan and Xue-Zhong Xu.
Author contributions: Ding W and Xu XZ contributed to conceptualization, resources, writing review and editing; Ding W, Xu XQ, Wu LL, Wang Q, Chen WW, Jiang HJ and Dong J contributed to methodology; Ding W contributed to investigation; Ding W and Xu XQ contributed to writing original draft preparation; Tan YL and Yan YM contributed to project administration; Wang YB contributed to validation and formal analysis; Dong J contributed to data curation; Yan YM contributed to supervision; Ding W, Tan YL and Xu XZ contributed to funding acquisition; Ding W, Xu XQ, Wu LL, Wang Q, Wang YQ, Chen WW, Tan YL, Wang YB, Jiang HJ, Dong J, Yan YM, Xu XZ contributed to the study and approved the submitted version of the manuscript.
Supported by the Changzhou Science and Techology Program, No. CJ20241048; Changzhou High-Level Medical Talents Training Project, No. 2022CZBJ105; Development Foundation of the Affiliated Hospital of Xuzhou Medical University, No. XYFC202304 and No. XYFM202307; and The Open Project of Jiangsu Provincial Key Laboratory of Laboratory Medicine, No. JSKLM-Z-2024-002.
Institutional review board statement: This study received approval from the Ethics Committee of the Affiliated Wujin Hospital of Jiangsu University (No. IRB-SOP-AF31).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Nanjing Medical University.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
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: Xue-Zhong Xu, Chief Physician, Department of General Surgery, Wujin Hospital Affiliated with Jiangsu University, No. 85 East Gehu Road, Changzhou 213162, Jiangsu Province, China. xxzdoctor@163.com
Received: May 16, 2025
Revised: June 8, 2025
Accepted: July 22, 2025
Published online: August 21, 2025
Processing time: 94 Days and 20 Hours
Core Tip

Core Tip: This study reveals that TSC22D1 plays a pivotal role in the progression of non-alcoholic fatty liver disease (NAFLD) fibrosis by promoting liver sinusoidal endothelial cell (LSEC) dysfunction and macrophage M1 polarization via the tumor necrosis factor-like weak inducer of apoptosis/fibroblast growth factor-inducible 14 signaling pathway. Through single-cell transcriptomic analysis and experimental validation, the authors demonstrate that TSC22D1 drives endothelial-mesenchymal transition and microvascularization in LSECs, while also enhancing pro-inflammatory responses in macrophages. Targeting TSC22D1 with adeno-associated virus serotype 8-short hairpin RNA alleviates liver fibrosis and inflammation in vivo, suggesting TSC22D1 as a promising therapeutic target for NAFLD. These findings provide novel insights into the mechanisms linking endothelial dysfunction, inflammation, and fibrosis in NAFLD.