Zhang MX, Wu C, Feng XX, Tian W, Zhao NH, Lu PP, Ding Q, Liu M. Celastrol alleviates esophageal stricture in rats by inhibiting NLR family pyrin domain containing 3 activation. World J Gastroenterol 2025; 31(23): 106949 [DOI: 10.3748/wjg.v31.i23.106949]
Corresponding Author of This Article
Mei Liu, MD, PhD, Professor, Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan 430030, Hubei Province, China. fliumei@126.com
Research Domain of This Article
Gastroenterology & Hepatology
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 Gastroenterol. Jun 21, 2025; 31(23): 106949 Published online Jun 21, 2025. doi: 10.3748/wjg.v31.i23.106949
Celastrol alleviates esophageal stricture in rats by inhibiting NLR family pyrin domain containing 3 activation
Miao-Xin Zhang, Chi Wu, Xin-Xia Feng, Wei Tian, Ning-Hui Zhao, Pan-Pan Lu, Qiang Ding, Mei Liu
Miao-Xin Zhang, Chi Wu, Wei Tian, Ning-Hui Zhao, Mei Liu, Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Xin-Xia Feng, Pan-Pan Lu, Qiang Ding, Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Author contributions: Liu M, Lu PP, and Ding Q designed the research study; Zhang MX, Wu Chi, Feng XX, Tian W, and Zhao NH performed the research.
Supported by National Natural Science Foundation of China, No. 82002609.
Institutional review board statement: The protocols were approved by the Ethics Committee of Tongji Medical College of Huazhong University of Science and Technology, No. S167.
Institutional animal care and use committee statement: All animal experimental procedures were approved by the Institutional Animal Care and Use Committee of Huazhong University of Science and Technology, No. 4016.
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: 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: Mei Liu, MD, PhD, Professor, Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan 430030, Hubei Province, China. fliumei@126.com
Received: March 12, 2025 Revised: April 23, 2025 Accepted: May 26, 2025 Published online: June 21, 2025 Processing time: 101 Days and 5.5 Hours
Abstract
BACKGROUND
The role of NLR family pyrin domain containing 3 (NLRP3) in post-endoscopic submucosal dissection (ESD) esophageal stricture remains incompletely understood. The effect of celastrol (CEL) on the prevention of esophageal strictures has not yet been investigated.
AIM
To explore the effect of CEL on the prevention of esophageal stricture in rats.
METHODS
NLRP3, interleukin (IL)-1β, and IL-18 mRNA levels were measured in patients’ tissues after esophageal ESD. NLRP3 expression in esophageal fibroblasts was determined using immunohistochemistry and immunofluorescence staining. Lentiviral transfection was used to induce NLRP3 overexpression and thioredoxin reductase 1 (TXNRD1) silencing. The CCK8 assay was used to determine the optimal CEL concentration. Reactive oxygen species (ROS) generation was detected via fluorescence and flow cytometry. Masson’s trichrome staining and barium esophagography were performed to assess collagen deposition and esophageal stenosis.
RESULTS
The mRNA levels of NLRP3 and IL-1β were higher in human tissues from the ESD resection bed than in normal esophageal mucosa. NLRP3 overexpression in primary rat esophageal fibroblasts led to high collagen 1 expression. Thus, NLRP3 participated in esophageal inflammation and tissue repair after ESD. Comparable to prednisolone, CEL significantly inhibited NLRP3 activation in vitro and in vivo, and esophageal strictures were markedly alleviated. Mechanistically, CEL upregulated TXNRD1 expression and reduced ROS production, thereby inhibiting NLRP3 expression. This effect was reversed by TXNRD1 silencing. Furthermore, TXNRD1 interacted with NLRP3 and promoted its ubiquitination.
CONCLUSION
CEL is a promising alternative therapeutic agent for the prevention of post-ESD esophageal strictures.
Core Tip: NLR family pyrin domain containing 3 (NLRP3) and interleukin-1β are increased in the endoscopic submucosal dissection resection bed of patients with esophageal neoplasms. Celastrol (CEL) prevented esophageal stricture in rats, and the effects were comparable to the positive control, prednisolone. Thioredoxin reductase 1 (TXNRD1) was increased by CEL in lipopolysaccharide plus adenosine triphosphate stimulated primary rat esophageal fibroblasts. Independent of its effect on reactive oxygen species, TXNRD1 interacts with NLRP3 and promotes its ubiquitination.
