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World J Gastrointest Surg. Nov 27, 2026; 18(11): 125359
Published online Nov 27, 2026. doi: 10.4240/wjgs.125359
Silencing of thrombospondin-1 prevents abdominal adhesion formation by reducing inflammation and oxidative stress
Hao-Chongyang Tong, Chang-Chun Ye, Zhi-Xing Zhang, Wen-Hao Lin, Chao Qu, Yuan-Yuan Gao, Jia-Hao Wang, Yun-Hua Wu, Yun-Ting Liu
Hao-Chongyang Tong, Zhi-Xing Zhang, Yun-Hua Wu, The Second Department of General Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710061, Shaanxi Province, China
Hao-Chongyang Tong, Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100069, China
Chang-Chun Ye, Wen-Hao Lin, Chao Qu, Yuan-Yuan Gao, Jia-Hao Wang, Department of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Yun-Ting Liu, Department of Endoscopy Center, Shaanxi Provincial People’s Hospital, Xi’an 710061, Shaanxi Province, China
Co-corresponding authors: Yun-Hua Wu and Yun-Ting Liu.
Author contributions: Tong HCY and Wu YH contributed to the study conception and the standardized adhesion model development; Gao YY and Wang JH contributed to the in vivo experiments performance including animal surgeries, grouping, and specimen collection; Lin WH and Zhang ZX contributed to conducting the small animal imaging and immunohistochemical staining; Qu C contributed to the Thbs-1-knockdown mouse model establishment and HMrSV5 cell lines; Ye CC and Tong HCY contributed to the multi-immunofluorescence staining, oxidative stress analysis, and Sirius red staining; Zhang ZX and Liu YT contributed to all the experimental data analysis including Nair’s scores, inflammatory scores, and reactive oxygen species formation; Ye CC contributed to the histological examinations including CK19 labeling and pathological assessments; Tong HC and Wu YH contributed to the interpretation of the molecular mechanisms and the manuscript drafting; Ye CC, Wu YH and Liu YT contributed to the revision of the manuscript for intellectual content. Wu YH and Liu YT contributed equally to this work as co-corresponding authors.
AI contribution statement: The audio file of the Core Tip was created solely using AI tools. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.
Supported by the National Natural Science Foundation of China, No. 82200563.
Institutional animal care and use committee statement: The animal experiments were approved by the Animal Ethics Committee of Xi’an Jiaotong University and have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments, No. XJTUAE2024-2003, July 4, 2024.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: The data used to support the findings of this study are available from the corresponding author upon request.
Corresponding author: Yun-Ting Liu, Department of Endoscopy Center, Shaanxi Provincial People’s Hospital, No. 256 West Youyi Road, Xi’an 710061, Shaanxi Province, China.
1529190353@qq.com
Received: July 6, 2026
Revised: August 24, 2026
Accepted: October 26, 2026
Published online: November 27, 2026
Processing time: 130 Days and 19 Hours
BACKGROUND
Intraperitoneal adhesions are fibrotic scars that form between abdominal organs after surgery and a major cause of postsurgical morbidity. Despite their clinical significance, the precise molecular mechanisms underlying their formation remain largely unclear, and standardized therapeutic strategies have yet to be established.
AIM
To investigate the role of thrombospondin-1 (Thbs-1) in peritoneal adhesion formation and evaluate its potential as a therapeutic target.
METHODS
A standardized peritoneal adhesion model was developed. Thbs-1-knockdown mice and HMrSV5 cell lines were established. Twenty-five mice were randomized to five treatment groups: Sham, negative control, sh-Thbs-1, normal saline, and Leu-Ser-Lys-Leu (LSKL). Adhesion severity was assessed 7 days post-surgery by Nair’s score and through immunohistochemistry, multi-immunofluorescence, and oxidative stress assays.
RESULTS
Thbs-1 was found to be highly expressed during adhesion formation. Both sh-Thbs-1 and LSKL treatments significantly attenuated adhesion formation, resulting in lower Nair’s and inflammatory scores. Mechanistically, Thbs-1 deficiency reduced reactive oxygen species (ROS) formation and promoted peritoneal mesothelial cell repair, as evidenced by CK19 labeling and Sirius red staining. In vitro, Thbs-1 knockdown protected HMrSV5 cells from rapid proliferation and oxidative stress damage.
CONCLUSION
Thbs-1 deficiency reduces adhesion formation by inhibiting inflammation and ROS production while promoting mesothelial repair. Accordingly, Thbs-1 represents a promising therapeutic target for postsurgical adhesions.
Core Tip: This study identifies thrombospondin-1 (Thbs-1) as a critical driver of postsurgical intraperitoneal adhesions. We demonstrate that Thbs-1 deficiency, achieved through genetic knockdown or pharmacological inhibition with Leu-Ser-Lys-Leu, significantly attenuates adhesion formation. The underlying mechanism involves the reduction of inflammation and oxidative stress alongside the promotion of peritoneal mesothelial cell repair. By uncovering this Thbs-1-mediated pathway, our findings offer a novel therapeutic strategy to mitigate postsurgical morbidity, highlighting Thbs-1 as a promising target for clinical intervention in abdominal surgery.
