ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1587860
This article is part of the Research TopicRole of Immune Cells in Fibrotic DiseasesView all articles
ER Stress Genes (COL1A1, LOXL2, VWF) Predicts IKK-16 as a Candidate Therapeutic Target for Colitis-related Inflammation and Fibrosis Suppression
Provisionally accepted
Ke Zhang1
Jiao Yang1Qing-Qing Yang1Jun-An Guo1Qian-Hui Huang1Chan Cui1Yue-Mei Wang1
Qiao-feng Wu1,2,3*
Jun-meng Wang1*- 1College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
- 2Acupuncture & Chronobiology Key Laboratory of Sichuan Province, Chengdu 611137, China, Chengdu, China
- 3Key Laboratory of Acupuncture for Senile Disease, Chengdu University of TCM, Ministry of Education,, Chengdu, China
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The role of endoplasmic reticulum stress (ERS) in the immune-inflammatory dysregulation and intestinal fibrosis associated with ulcerative colitis (UC) remains unclear. This study aims to identify ERS-related genes involved in UC fibrosis and explore potential therapeutic targets. Methods: Differentially expressed ERS-related genes (DE-ERGs) were identified through comprehensive analysis of public datasets. Machine learning methods screened VWF, MZB1, COL1A1, and LOXL2 as key regulators. Immune infiltration analysis, protein-protein interaction (PPI) network analysis, and gene set variation analysis (GSVA) were performed to clarify their roles in UC fibrosis. Drug prediction was conducted using the Connectivity Map (CMap) database, supplemented by a literature review. Results: The predicted drugs were ranked based on their binding affinities as follows: IKK-16 > Quercetin > Curcumin > Resveratrol > Budesonide > Trimebutine > Colchicine > Betamethasone > Pioglitazone > Metformin. IKK-16 showed the highest binding affinity for treating UC fibrosis. COL1A1, LOXL2, and VWF were identified as key drivers of UC intestinal fibrosis, supported by immune infiltration and PPI network analyses. Discussion: These results suggest that ERS-related genes, particularly COL1A1, LOXL2, and VWF, may regulate UC fibrosis through interactions with immune cells. IKK-16 shows promise as a therapeutic agent. These findings provide new insights into UC pathogenesis and potential clinical treatment strategies.
Keywords: intestinal fibrosis, Inflammation, er stress, molecular docking, Bioinformatics analysis, Immune infiltration
Received: 05 Mar 2025; Accepted: 29 May 2025.
Copyright: © 2025 Zhang, Yang, Yang, Guo, Huang, Cui, Wang, Wu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qiao-feng Wu, College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, Sichuan Province, China
Jun-meng Wang, College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, Sichuan Province, China
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