Inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis, is a lifelong disease that manifests with chronic intestinal inflammation, sequential fibrosis, and an increased risk of colitis-associated colon cancer (CAC). The combined effects of genetic, immunological, environmental, and microbial factors render it difficult to determine the specific mechanism underlying the induction and perpetuation of IBD. Various animal models of IBD have contributed enormously to the understanding of IBD pathogenesis in terms of genomics, transcriptomics, proteomics, microbiome, and drug development of novel therapeutics. Although comprehensive research on IBD has been enabled by advanced technologies, such as genetically engineered models, there is a great need to develop relevant in vivo models of colitis and fibrosis. Here, we review 4 categories of animal models of acute and chronic intestinal inflammation, fibrosis, and CAC: chemically induced, genetically engineered, T cell transfer, and spontaneous gene mutation models.
Citations
Citations to this article as recorded by
Refined photobiomodulation therapy ameliorates inflammatory bowel disease via modulation of immune pathways and gut microbiota Lee So Maeng, Jung Hwan Yoon, Bom Yee Chung, Kyung Jin Seo, Hae Kyung Lee, Moon Gyu Chung, Won Sang Park, Hiun Suk Chae Journal of Photochemistry and Photobiology B: Biology.2026; 274: 113330. CrossRef
Estrogen Receptor β Activation Mitigates Colitis-associated Intestinal Fibrosis via Inhibition of TGF-β/Smad and TLR4/MyD88/NF-κB Signaling Pathways Fangmei Ling, Yidong Chen, Junrong Li, Mingyang Xu, Gengqing Song, Lei Tu, Huan Wang, Shuang Li, Liangru Zhu Inflammatory Bowel Diseases.2025; 31(1): 11. CrossRef
Leveraging Organ‐on‐Chip Models to Investigate Host–Microbiota Dynamics and Targeted Therapies for Inflammatory Bowel Disease Tim Kaden, Raquel Alonso‐Román, Johannes Stallhofer, Mark S. Gresnigt, Bernhard Hube, Alexander S. Mosig Advanced Healthcare Materials.2025;[Epub] CrossRef
Adiponectin deficiency prevents chronic colitis-associated colonic fibrosis via inhibiting CXCL13 production Haitao Xiao, Tianhang Xing, Miao Qiu, Guangtao Zhang, Gongli Yang, Wenke Chen, Die Hu, Deao Xue, Jiao Peng, Bin Du Journal of Advanced Research.2025; 76: 639. CrossRef
Fructosyl-mangiferin ameliorates dextran sulfate sodium-induced colitis in mice via the STAT3/M1/Th17 axis Penghong Xu, Yuping Qian, Guo Xu, Jianlin Chu, Bingfang He Phytomedicine.2025; 139: 156475. CrossRef
S1PR1-biased activation drives the resolution of endothelial dysfunction-associated inflammatory diseases by maintaining endothelial integrity Huaping Zheng, Jingjing Yu, Luhua Gao, Kexin Wang, Zheng Xu, Zhen Zeng, Kun Zheng, Xiaoju Tang, Xiaowen Tian, Qing Zhao, Jie Zhao, Huajing Wan, Zhongwei Cao, Kang Zhang, Jingqiu Cheng, Jürgen Brosius, Hu Zhang, Wei Li, Wei Yan, Zhenhua Shao, Fengming Luo, Nature Communications.2025;[Epub] CrossRef
Groundwater Nitrate Contamination and its Effect on Human Health: A Review Indra Jeet Chaudhary, Ratna Chauhan, Sanjay Sarjerao Kale, Suresh Gosavi, Dheeraj Rathore, Vinay Dwivedi, Sunita Singh, Virendra Kumar Yadav Water Conservation Science and Engineering.2025;[Epub] CrossRef
Standardization of a Preclinical Colon Cancer Model in Male and Female BALB/c Mice: Macroscopic and Microscopic Characterization from Pre-Neoplastic to Tumoral Lesions Elizabeth Correa, Juan Pablo Rendón, Vanesa Bedoya-Betancur, Juliana Montoya, Julian Muñoz Duque, Tonny W. Naranjo Biomedicines.2025; 13(4): 939. CrossRef
Metabolic Disorders and Inflammatory Bowel Diseases Hye Kyung Hyun, Jae Hee Cheon Gut and Liver.2025; 19(3): 307. CrossRef
A review on ulcerative colitis induction models and the protective mechanism of carbon quantum dots as a novel anti-inflammatory and anti-ulcer agent Mohammad Beiranvand, Gholamreza Dehghan Discover Pharmaceutical Sciences.2025;[Epub] CrossRef
Oral–gut microbiome axis in a Korean cohort with inflammatory bowel disease and ankylosing spondylitis (INTEGRATE): a prospective and observational study protocol Hyun Sik Kim, Bo-Hyung Kim, Bora Nam, Shin Ju Oh, Soo-Kyung Park, Sang Won Lee, Jae-Yun Lee, Sungsin Jo, Yeon-Ah Lee, June-Young Lee, Dong Il Park, Tae-Hwan Kim, Chang Kyun Lee BMJ Open.2025; 15(8): e092075. CrossRef
Role of physical exercise, vagal nerve stimulation, and vagotomy in inflammatory bowel disease Alda Cassia Alves da Silva, Juliana Soares Severo, Brenda Lois Barros dos Santos, Heron Silva Soares, Jorddam Almondes Martins, Rodrigo Soares Pereira Lima, Kalinne Kelly Lima Gadelha, Francisco Leonardo Torres-Leal, Paulo Correia-de-Sá, Pedro Jorge Calda World Journal of Gastroenterology.2025;[Epub] CrossRef
From AI-Assisted In Silico Computational Design to Preclinical In Vivo Models: A Multi-Platform Approach to Small Molecule Anti-IBD Drug Discovery Joya Datta Ripa, Sarfaraz Ali, Matt Field, John Smithson, Phurpa Wangchuk Pharmaceuticals.2025; 18(10): 1536. CrossRef
A Comprehensive Narrative Review of Potential Gastrointestinal Adverse Effects From Micro(nano) Plastic Exposure Priyata Dutta, Sana Rabeeah, Alejandra Vargas, Edward C. Oldfield, David A. Johnson Clinical Gastroenterology and Hepatology.2025;[Epub] CrossRef
Effect of Gut Microbiota Alteration on Colorectal Cancer Progression in an In Vivo Model: Histopathological and Immunological Evaluation Juliana Montoya Montoya, Elizabeth Correa Gómez, Jorge Humberto Tabares Guevara, Julián Camilo Arango Rincón, Tonny Williams Naranjo Preciado Current Issues in Molecular Biology.2025; 48(1): 15. CrossRef
Approaches, Strategies and Procedures for Identifying Anti-Inflammatory Drug Lead Molecules from Natural Products Tenzin Jamtsho, Karma Yeshi, Matthew J. Perry, Alex Loukas, Phurpa Wangchuk Pharmaceuticals.2024; 17(3): 283. CrossRef
Strategies for targeting cytokines in inflammatory bowel disease Markus F. Neurath Nature Reviews Immunology.2024; 24(8): 559. CrossRef
Inhibiting the cGAS-STING Pathway in Ulcerative Colitis with Programmable Micelles Saji Uthaman, Shadi Parvinroo, Ansuja Pulickal Mathew, Xinglin Jia, Belen Hernandez, Alexandra Proctor, Karuna Anna Sajeevan, Ariel Nenninger, Mary-Jane Long, In-Kyu Park, Ratul Chowdhury, Gregory J. Phillips, Michael J. Wannemuehler, Rizia Bardhan ACS Nano.2024; 18(19): 12117. CrossRef
Targeting cyclooxygenase-2 for chemoprevention of inflammation-associated intestinal carcinogenesis: An update Kyung-Soo Chun, Eun-Hee Kim, Do-Hee Kim, Na-Young Song, Wonki Kim, Hye-Kyung Na, Young-Joon Surh Biochemical Pharmacology.2024; 228: 116259. CrossRef
Lactobacillus paracasei Jlus66 relieves DSS-induced ulcerative colitis in a murine model by maintaining intestinal barrier integrity, inhibiting inflammation, and improving intestinal microbiota structure Fazheng Yu, Xiaoxu Wang, Honglin Ren, Jiang Chang, Jian Guo, Zhaoqi He, Ruoran Shi, Xueyu Hu, Yuanyuan Jin, Shiying Lu, Yansong Li, Zengshan Liu, Pan Hu European Journal of Nutrition.2024; 63(6): 2185. CrossRef
Predictors of histologic remission in patients with biologic-naïve, moderate-to-severe ulcerative colitis treated with first-line biologic agents and small-molecule drugs: a single-center, retrospective cohort study Kijae Jo, Kwang Woo Kim, Hyun Jung Lee, Jong Pil Im, Joo Sung Kim, Seong-Joon Koh Intestinal Research.2024; 22(4): 453. CrossRef
Interventional Effects of Lactobacillus plantarum Hfy04 Isolated from Naturally Fermented Yak Yogurt on Oxazolone-Induced Colitis in BALB/c Mice Haitao Zheng, Xiaoli Ping, Ruizi Wu, Cen Lei, Huijia Mao, Yanni Pan, Yongpeng He, Xin Zhao International Journal of Pharmacology.2024; 20(5): 817. CrossRef
Inhibition of myeloperoxidase by food-derived peptides: A review of current research and future prospects Fai-Chu Wong, Yit-Lai Chow, Sheri-Ann Tan, Lingmin Tian, Weibin Bai, Tsun-Thai Chai Food Bioscience.2024; 60: 104458. CrossRef
Deciphering Microbial Composition in Patients with Inflammatory Bowel Disease: Implications for Therapeutic Response to Biologic Agents Orazio Palmieri, Fabrizio Bossa, Stefano Castellana, Tiziana Latiano, Sonia Carparelli, Giuseppina Martino, Manuel Mangoni, Giuseppe Corritore, Marianna Nardella, Maria Guerra, Giuseppe Biscaglia, Francesco Perri, Tommaso Mazza, Anna Latiano Microorganisms.2024; 12(7): 1260. CrossRef
Protective effect of freeze-dried extract of Persicaria bistorta Samp. on acetic acid-induced colitis model in rats: Involvement of nitric oxide and opioid system Niusha Esmaealzadeh, Amirhossein Abdolghaffari, Maryam Baeeri, Maede Hasanpour, Mehrdad Iranshahi, Cristina Santarcangelo, Mahdi Gholami, Roodabeh Bahramsoltani Inflammopharmacology.2024; 32(6): 3845. CrossRef
Advances in Vascular Diagnostics using Magnetic Particle Imaging (MPI) for Blood Circulation Assessment Marisa O Pacheco, Isabelle K Gerzenshtein, Whitney L Stoppel, Carlos M Rinaldi‐Ramos Advanced Healthcare Materials.2024;[Epub] CrossRef
Immunomodulatory Effects of a Probiotic Mixture: Alleviating Colitis in a Mouse Model through Modulation of Cell Activation Markers and the Gut Microbiota Hye-Myung Ryu, S. M. Shamsul Islam, Bushra Riaz, Hasan M. Sayeed, Bunsoon Choi, Seonghyang Sohn International Journal of Molecular Sciences.2024; 25(16): 8571. CrossRef
Immuno-therapeutic and prophylactic potential of Trichinella spiralis antigens for inflammatory bowel diseases Majed H. Wakid, Walaa A. El Kholy, Muslimah N. Alsulami, Eman S. El-Wakil Food and Waterborne Parasitology.2024; 37: e00248. CrossRef
Development of a novel complex inflammatory bowel disease mouse model: Reproducing human inflammatory bowel disease etiologies in mice Sun-Min Seo, Na-Won Kim, Eun-Seon Yoo, Ji-Hun Lee, Ah-Reum Kang, Han-Bi Jeong, Won-Yong Shim, Dong-Hyun Kim, Young-Jun Park, Kieun Bae, Kyong-Ah Yoon, Yang-Kyu Choi, Pradeep Dudeja PLOS ONE.2024; 19(11): e0311310. CrossRef
Gut Microbiome and Colorectal Cancer Tae-Geun Gweon The Korean Journal of Gastroenterology.2023; 82(2): 56. CrossRef
Mitochondrial dysfunctions in T cells: focus on inflammatory bowel disease Hoyul Lee, Jae-Han Jeon, Eun Soo Kim Frontiers in Immunology.2023;[Epub] CrossRef
The use of biologic agents including anti-tumor necrosis factor monoclonal antibodies followed by anti-integrins and anti-interleukins has drastically changed the treatment paradigm of Crohn’s disease (CD) by improving clinical symptoms and mucosal healing. However, up to 70% of CD patients still eventually undergo surgery mainly due to fibrostenotic strictures. There are no specific anti-fibrotic drugs yet. This review comprehensively addresses the mechanism, prediction, diagnosis and treatment of the fibrostenotic strictures in CD. We also introduce promising anti-fibrotic agents which may be available in the near future and summarize challenges in developing novel therapies to treat fibrostenotic strictures in CD.
Citations
Citations to this article as recorded by
Role of Endoscopic Ultrasound in the Diagnosis and Management of Complications of Inflammatory Bowel Disease Jay Bapaye, Saurabh Chandan, Gursimran S. Kochhar Gastrointestinal Endoscopy Clinics of North America.2025; 35(1): 235. CrossRef
Eicosatetraynoic Acid Regulates Profibrotic Pathways in an Induced Pluripotent Stem Cell–Derived Macrophage-Human Intestinal Organoid Model of Crohn’s Disease Ingrid Jurickova, Benjamin W Dreskin, Elizabeth Angerman, Erin Bonkowski, Jack Nguyen, Richard Villarreal, Kentaro Tominaga, Kentaro Iwasawa, Tzipi Braun, Takanori Takebe, Michael A Helmrath, Yael Haberman, James M Wells, Lee A Denson Journal of Crohn's and Colitis.2025;[Epub] CrossRef
Letter: The Simple Endoscopic Score for Predicting Crohn's Disease Progression—Not as Simple as It Sounds Ziheng Calvin Xu, Ethan Tan, Mayur Garg Alimentary Pharmacology & Therapeutics.2025; 61(9): 1585. CrossRef
Circular RNAs in inflammatory bowel disease: a review of mechanisms, biomarkers and therapeutic potential Le Yang, Huahui Li, Min Tang, Lingnan He, Lijun Yang Frontiers in Immunology.2025;[Epub] CrossRef
Tumor Necrosis Factor-Like Ligand 1A/Death Receptor 3 Signaling Regulates the Generation of Pathogenic T Helper 9 Cells in Experimental Crohn’s Disease Paola Menghini, Ludovica F. Buttó, Adrian Gomez-Nguyen, Natalia Aladyshkina, Kristine-Ann Buela, Abdullah Osme, Ricky Chan, Hannah L. Wargo, Stefania De Santis, Giorgos Bamias, Theresa T. Pizarro, Fabio Cominelli Gastroenterology.2025; 169(5): 892. CrossRef
ECM formation and degradation during fibrosis, repair, and regeneration Alejandro E. Mayorca-Guiliani, Diana Julie Leeming, Kim Henriksen, Joachim Høg Mortensen, Signe Holm Nielsen, Quentin M. Anstee, Arun J. Sanyal, Morten A. Karsdal, Detlef Schuppan npj Metabolic Health and Disease.2025;[Epub] CrossRef
Therapeutic potential of Janus kinase inhibitors for the management of fibrosis in inflammatory bowel disease Jie Su, Dalia A Lartey, Gaia Zanella, Lukas J A C Hawinkels, Gianluca Matteoli, Mark Löwenberg, Marieke C Barnhoorn Journal of Crohn's and Colitis.2025;[Epub] CrossRef
Disease-Specific Novel Role of Growth Differentiation Factor 15 in Organ Fibrosis Harshal Sawant, Alip Borthakur International Journal of Molecular Sciences.2025; 26(12): 5713. CrossRef
Molecular Basis of Chronic Intestinal Wall Fibrosis in Inflammatory Bowel Diseases Patrycja Sputa-Grzegrzolka, Anna Socha-Banasiak, Piotr Dziegiel, Bartosz Kempisty International Journal of Molecular Sciences.2025; 26(12): 5754. CrossRef
Serological assessment of PRO-C16 (type XVI collagen formation) reflects intestinal fibrostenotic strictures in patients with crohn’s disease Joachim H. Mortensen, M. Lindholm, L. Langholm, P. Giuffrida, D. Ruane, T. Manon-Jensen, G. Mazza, F. Caprioli, L. Pastorelli, A-C. Bay-Jensen, M. Pinzani, M. A. Karsdal, A. Di Sabatino BMC Gastroenterology.2025;[Epub] CrossRef
Development and validation of a novel model based on clinical characteristics to predict natural disease course progression in patients with stricturing Crohn’s disease Yu Wang, Xiaomin Wu, Weitong Gao, Xiaolong Chen, Haoyin Chen, Zishan Liu, Yao Zhang, Yubei Gu, Ren Mao Therapeutic Advances in Gastroenterology.2025;[Epub] CrossRef
Appropriate Use and Complications of Corticosteroids in Inflammatory Bowel Disease: A Comprehensive Review Joseph D. Feuerstein, David T. Rubin, Faten N. Aberra, Andres J. Yarur, Lisa Malter Clinical Gastroenterology and Hepatology.2025; 23(12): 2068. CrossRef
Insights into the Molecular Mechanisms and Novel Therapeutic Strategies of Stenosis Fibrosis in Crohn’s Disease Yuan Zhou, Huiping Chen, Qinbo Wang, Guozeng Ye, Yingjuan Ou, Lihong Huang, Xia Wu, Jiaxi Fei Biomedicines.2025; 13(7): 1777. CrossRef
Beyond inflammation: what drives the self-perpetuating cycle of fibrosis in IBD? Yutong Wei, Zhou Zhou, Shiyu Xiao Annals of Medicine.2025;[Epub] CrossRef
Transglutaminase 2 in chronic inflammation and fibrosis – a potential novel therapy for stricturing Crohn’s disease Jyotsna Chandra, Gail A. West, Yan Wang, Afshin Khan, Florian Rieder Expert Review of Clinical Immunology.2025; 21(11): 1555. CrossRef
Tolerability and effect of inhibiting microfibrillar-associated protein 4 in small intestinal anastomotic healing Rasmus Refshauge Andresen, Jesper Brandt Pedersen, Paula Frederikke Hellsegg Grünfeld, Charlotte Skoie Nielsen, Anna Lings Kjelgaard, Anders Frederik Højer Kolind, Nils Grimm, Kasper Emil Rosenbech, Henriette Kirkeby Høiberg, Johanne Kalland, Mie Dilling, Scientific Reports.2025;[Epub] CrossRef
Elucidating a Myofibroblast-dominated Fibrotic Niche in Crohn’s Disease-associated Fibrostenosis Through High-resolution Spatial Transcriptomics Da Zhang, Xinru Zou, Mengjia He, Shibo Sun, Anqi Yu, Jintao Shi, Ting Ouyang, Xiaoxia Lin, Hui Yang, Lan Bai, Kai Sun, Jiaolong Shi, Fangting Wu, Wenting Xie, Jingyan Li, Fang Xie Cellular and Molecular Gastroenterology and Hepatology.2025; : 101701. CrossRef
Histological Image-based Ensemble Model to Identify Myenteric Plexitis and Predict Endoscopic Postoperative Recurrence in Crohn’s Disease: A Multicentre, Retrospective Study Yuexin Wang, Qi He, Danhua Yao, Yuhua Huang, Wenwen Xia, Weilin Chen, Zhe Cui, Yousheng Li Journal of Crohn's and Colitis.2024; 18(5): 727. CrossRef
Contemporary Imaging Assessment of Strictures and Fibrosis in Crohn Disease, With Focus on Quantitative Biomarkers: From the AJR Special Series on Imaging of Fibrosis Jordi Rimola, Kim J. Beek, Ingrid Ordás, Krisztina B. Gecse, Míriam Cuatrecasas, Jaap Stoker American Journal of Roentgenology.2024;[Epub] CrossRef
Surgical Emergencies in Inflammatory Bowel Disease John Van Eaton, Quinton M. Hatch Surgical Clinics of North America.2024; 104(3): 685. CrossRef
Fibrosis in IBD: from pathogenesis to therapeutic targets Florian Rieder, Pranab K Mukherjee, William J Massey, Yan Wang, Claudio Fiocchi Gut.2024; 73(5): 854. CrossRef
Enter the Matrix: Fibroblast-immune interactions shape ECM deposition in health and disease. Anthony Altieri, Grace V. Visser, Matthew B. Buechler F1000Research.2024; 13: 119. CrossRef
Preventing fibrosis in IBD: update on immune pathways and clinical strategies Jie Wang, Bo Yang, Jyotsna Chandra, Andrei Ivanov, J. Mark Brown, Florian Rieder Expert Review of Clinical Immunology.2024; 20(7): 727. CrossRef
Intestinal strictures in Crohn's disease: An update from 2023 Zishan Liu, Zhuoyan Huang, Yu Wang, Shanshan Xiong, Sinan Lin, Jinshen He, Jinyu Tan, Caiguang Liu, Xiaomin Wu, Jing Nie, Weidong Huang, Yao Zhang, Longyuan Zhou, Ren Mao United European Gastroenterology Journal.2024; 12(6): 802. CrossRef
Naringin Alleviates Intestinal Fibrosis by Inhibiting ER Stress–Induced PAR2 Activation Jinguo Liu, Lei Xu, Li Wang, Qianqian Wang, Liangliang Yu, Shuo Zhang Inflammatory Bowel Diseases.2024; 30(11): 1946. CrossRef
Characterization of patient-derived intestinal organoids for modelling fibrosis in Inflammatory Bowel Disease Ilaria Laudadio, Claudia Carissimi, Noemi Scafa, Alex Bastianelli, Valerio Fulci, Alessandra Renzini, Giusy Russo, Salvatore Oliva, Roberta Vitali, Francesca Palone, Salvatore Cucchiara, Laura Stronati Inflammation Research.2024; 73(8): 1359. CrossRef
Efficacy and Safety of Endoscopic Stricturotomy in Inflammatory Bowel Disease-Related Strictures: A Systematic Review and Meta-Analysis Fouad Jaber, Laith Numan, Mohammed Ayyad, Mohamed Abuelazm, Muhammad Imran, Majd M. AlBarakat, Aya M. Aboutaleb, Ubaid Khan, Saqr Alsakarneh, Mohammad Bilal Digestive Diseases and Sciences.2024; 69(11): 4152. CrossRef
A Comprehensive Multidisciplinary Approach to Diagnosing Chronic Inflammatory Bowel Diseases: Integration of Clinical, Endoscopic, and Imaging Modalities Clelia Cicerone, Ferdinando D’Amico, Mariangela Allocca, Alessandra Zilli, Tommaso Lorenzo Parigi, Silvio Danese, Federica Furfaro Diagnostics.2024; 14(14): 1530. CrossRef
Management of Crohn’s disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023 Jia-Feng Wu, Hsu-Heng Yen, Horng-Yuan Wang, Ting-An Chang, Chung-Hsin Chang, Chen-Wang Chang, Te-Hsin Chao, Jen-Wei Chou, Yenn-Hwei Chou, Chiao-Hsiung Chuang, Wen-Hung Hsu, Tzu-Chi Hsu, Tien-Yu Huang, Tsung-I Hung, Puo-Hsien Le, Chun-Che Lin, Chun-Chi Lin Intestinal Research.2024; 22(3): 250. CrossRef
Enfermedad de Crohn estenosante y endometriosis intestinal: coexistencia inusual F. Carvajal, F. López, P. Núñez, L. Contreras, R. Quera Revista de Gastroenterología de México.2024; 89(4): 550. CrossRef
Muscular hyperplasia in Crohn’s disease strictures: through thick and thin Ido Veisman, William J. Massey, Idan Goren, Weiwei Liu, Gaurav Chauhan, Florian Rieder American Journal of Physiology-Cell Physiology.2024; 327(3): C671. CrossRef
Inhibition of intestinal inflammation and fibrosis by Scutellaria Baicalensis georgi and Boswellia serrata in human epithelial cells and fibroblasts Ilaria Laudadio, Beatrice Leter, Francesca Palone, Salvatore Cucchiara, Claudia Carissimi, Noemi Scafa, Daniela Secci, Roberta Vitali, Laura Stronati Immunity, Inflammation and Disease.2024;[Epub] CrossRef
How Protein Depletion Balances Thrombosis and Bleeding Risk in the Context of Platelet’s Activatory and Negative Signaling Hector Montecino-Garrido, Andrés Trostchansky, Yolanda Espinosa-Parrilla, Iván Palomo, Eduardo Fuentes International Journal of Molecular Sciences.2024; 25(18): 10000. CrossRef
Stricturing Crohn’s disease and intestinal endometriosis: An unusual coexistence F. Carvajal, F. López, P. Núñez, L. Contreras, R. Quera Revista de Gastroenterología de México (English Edition).2024; 89(4): 550. CrossRef
The Versatile Role of Peroxisome Proliferator-Activated Receptors in Immune-Mediated Intestinal Diseases Edit Posta, Istvan Fekete, Istvan Varkonyi, Eva Zold, Zsolt Barta Cells.2024; 13(20): 1688. CrossRef
Eosinophils mitigate intestinal fibrosis while promoting inflammation in a chronic DSS colitis model and co-culture model with fibroblasts Inge Jacobs, Sara Deleu, Bo-Jun Ke, Jonathan Cremer, Ellen Dilissen, Gert De Hertogh, Tobie Martens, Pieter Vanden Berghe, Gianluca Matteoli, Séverine Vermeire, Christine Breynaert, Tim Vanuytsel, Bram Verstockt Scientific Reports.2024;[Epub] CrossRef
Endoskopische und chirurgische Behandlung intestinaler Stenosen im Zusammenhang mit chronisch-entzündlichen Darmerkrankungen Tabea Pfister, Jonas Zbinden, Benjamin Misselwitz, Emanuel Burri, Florian Rieder, Lukas Brügger, Reiner Wiest Schweizer Gastroenterologie.2024; 5(4): 103. CrossRef
Enter the Matrix: Fibroblast-immune cell interactions shape extracellular matrix deposition in health and disease. Anthony Altieri, Grace V. Visser, Matthew B. Buechler F1000Research.2024; 13: 119. CrossRef
Korean clinical practice guidelines on biologics for moderate to severe Crohn’s disease Seong-Joon Koh, Sung Noh Hong, Soo-Kyung Park, Byong Duk Ye, Kyeong Ok Kim, Jeong Eun Shin, Yong Sik Yoon, Hong Sub Lee, Sung Hoon Jung, Miyoung Choi, Soo-Young Na, Chang Hwan Choi, Joo Sung Kim Intestinal Research.2023; 21(1): 43. CrossRef
Targeting integrin pathways: mechanisms and advances in therapy Xiaocong Pang, Xu He, Zhiwei Qiu, Hanxu Zhang, Ran Xie, Zhiyan Liu, Yanlun Gu, Nan Zhao, Qian Xiang, Yimin Cui Signal Transduction and Targeted Therapy.2023;[Epub] CrossRef
Adipokine C1q/Tumor Necrosis Factor- Related Protein 3 (CTRP3) Attenuates Intestinal Inflammation Via Sirtuin 1/NF-κB Signaling Huimin Yu, Zixin Zhang, Gangping Li, Yan Feng, Lingling Xian, Fatemeh Bakhsh, Dongqing Xu, Cheng Xu, Tyrus Vong, Bin Wu, Florin M. Selaru, Fengyi Wan, Mark Donowitz, G. William Wong Cellular and Molecular Gastroenterology and Hepatology.2023; 15(4): 1000. CrossRef
Burden of disease among patients with prevalent Crohn’s disease: results from a large German sickness fund Evi Zhuleku, Beatriz Antolin-Fontes, Andras Borsi, Riikka Nissinen, Ivana Bravatà, Jennifer Norma Barthelmes, Jennifer Lee, Alun Passey, Daniel Wirth, Ulf Maywald, Bernd Bokemeyer, Thomas Wilke, Marco Ghiani International Journal of Colorectal Disease.2023;[Epub] CrossRef
Fibro-Stenosing Crohn’s Disease: What Is New and What Is Next? Virginia Solitano, Arianna Dal Buono, Roberto Gabbiadini, Marek Wozny, Alessandro Repici, Antonino Spinelli, Stefania Vetrano, Alessandro Armuzzi Journal of Clinical Medicine.2023; 12(9): 3052. CrossRef
How to Evaluate Fibrosis in IBD? Helena Tavares de Sousa, Fernando Magro Diagnostics.2023; 13(13): 2188. CrossRef
Smooth muscle dysfunction in the pre-inflammation site in stenotic Crohn’s-like colitis: implication of mechanical stress in bowel dysfunction in gut inflammation John C. Johnson, Ramasatyaveni Geesala, Ke Zhang, You-Min Lin, Amosy E. M’Koma, Xuan-Zheng Shi Frontiers in Physiology.2023;[Epub] CrossRef
Risk and incidence of colorectal stricture progressing to colorectal neoplasia in patients with inflammatory bowel disease: a systematic review and meta-analysis Yanrong Zhan, Xianwen Cheng, Pingping Mei, Jiyun Wu, Yan Ou, Yaping Cui European Journal of Gastroenterology & Hepatology.2023; 35(10): 1075. CrossRef
P2X7 Receptor Regulates Collagen Expression in Human Intestinal Fibroblasts: Relevance in Intestinal Fibrosis Lluis Lis-López, Cristina Bauset, Marta Seco-Cervera, Dulce Macias-Ceja, Francisco Navarro, Ángeles Álvarez, Juan Vicente Esplugues, Sara Calatayud, Maria Dolores Barrachina, Dolores Ortiz-Masià, Jesús Cosín-Roger International Journal of Molecular Sciences.2023; 24(16): 12936. CrossRef
Solitary lipoma of ileocaecal valve mimicking Crohn's disease: A case report of a challenging diagnosis for a rare benign tumor of the intestinal tract Debaibi Mehdi, Talbi Skander, Trigui Racem, Nejib Fatma, Guermazi Ahmed, Chouchen Adnen International Journal of Surgery Case Reports.2023; 110: 108696. CrossRef
Role of the epithelial barrier in intestinal fibrosis associated with inflammatory bowel disease: relevance of the epithelial-to mesenchymal transition Dulce C. Macias-Ceja, M. Teresa Mendoza-Ballesteros, María Ortega-Albiach, M. Dolores Barrachina, Dolores Ortiz-Masià Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef
Distribution of small bowel involvement and its association with clinical outcomes in patients with Crohn’s disease Jin Park, Hae Young Kim, Yoon Jin Lee, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Nayoung Kim, Dong Ho Lee Medicine.2023; 102(40): e35040. CrossRef
Downregulation of Heat Shock Protein 72 Contributes to Fibrostenosis in Crohn’s Disease Seung Won Kim, Jae-Young Lee, Han Cheol Lee, Jae Bum Ahn, Ji Hyung Kim, I Seul Park, Jae Hee Cheon, Duk Hwan Kim Gut and Liver.2023; 17(6): 905. CrossRef
Association of Circulating Fibrocytes With Fibrostenotic Small Bowel Crohn’s Disease Aito Ueno, Humberto B Jijon, Richard Peng, Steven Sparksman, Barbara Mainoli, Alexis Filyk, Yan Li, Stephanie Wilson, Kerri Novak, Remo Panaccione, Simon Hirota, Antoine Dufour, Cathy Lu, Paul L Beck Inflammatory Bowel Diseases.2022; 28(2): 246. CrossRef
Revisiting fibrosis in inflammatory bowel disease: the gut thickens Silvia D’Alessio, Federica Ungaro, Daniele Noviello, Sara Lovisa, Laurent Peyrin-Biroulet, Silvio Danese Nature Reviews Gastroenterology & Hepatology.2022; 19(3): 169. CrossRef
Clinical factors to predict flare-up in patients with inflammatory bowel disease during international air travel: A prospective study Jihye Park, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Nayoung Kim, Dong Ho Lee, Alaa El-Hussuna PLOS ONE.2022; 17(1): e0262571. CrossRef
Diagnosis and Psychotherapeutic Needs by Early Maladaptive Schemas in Patients With Inflammatory Bowel Disease Cornelia Rada, Dan Gheonea, Cristian George Ţieranu, Denisa Elena Popa Frontiers in Psychology.2022;[Epub] CrossRef
Network Pharmacology-Based Strategy to Identify the Pharmacological Mechanisms of Pulsatilla Decoction against Crohn’s Disease Jinguo Liu, Lu Zhang, Zhaojun Wang, Shanshan Chen, Shuyan Feng, Yujin He, Shuo Zhang Frontiers in Pharmacology.2022;[Epub] CrossRef
Is radiological healing alone enough? ‘Can’t take my eyes off’ the mucosa Su Hyun Park, Sang Hyoung Park The Korean Journal of Internal Medicine.2022; 37(3): 551. CrossRef
Intestinal Ultrasound for Differentiating Fibrotic or Inflammatory Stenosis in Crohn’s Disease: A Systematic Review and Meta-analysis Chenjing Xu, Wenyu Jiang, Lu Wang, Xiaqiong Mao, Ziping Ye, Hongjie Zhang Journal of Crohn's and Colitis.2022; 16(9): 1493. CrossRef
Continued Postoperative Use of Tumor Necrosis Factor-α Inhibitors for the Prevention of Crohn’s Disease Recurrence Jongwook Yu, Hye Kyung Hyun, Jihye Park, Eun Ae Kang, Soo Jung Park, Jae Jun Park, Tae Il Kim, Won Ho Kim, Jae Hee Cheon Gut and Liver.2022; 16(3): 414. CrossRef
Use of Intraoperative Calibration Spheres for Endoluminal Stricture Assessment to Facilitate Heineke-Mikulicz Strictureplasty in Diffuse Stricturing Crohn’s Jejunoileitis Leonardo C. Duraes, Chun Hin Angus Lee, Stefan D. Holubar Diseases of the Colon & Rectum.2022; 65(7): e741. CrossRef
Medication Adherence in Korean Patients with Inflammatory Bowel
Disease and Its Associated Factors Kyunghwan Oh, Eun Ja Kwon, Jeong Hye Kim, Kyuwon Kim, Jae Yong Lee, Hee Seung Hong, Seung Wook Hong, Jin Hwa Park, Sung Wook Hwang, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Jeong Yun Park, Sang Hyoung Park The Ewha Medical Journal.2022; 45(2): 35. CrossRef
Frequency of Anastomosis Leak in Primary Repair in Ileal Perforation Muhammad Shah, Muhammad Iftikhar, Yousaf Jan, Shehzad Akbar Khan, Shimee Shahzadi Journal of Gandhara Medical and Dental Science.2022; 9(3): 39. CrossRef
Bowel-Preserving Surgery for Diffuse Stricturing Crohn’s Jejunoileitis Leonardo C. Duraes, Stefan D. Holubar Diseases of the Colon & Rectum.2022; 65(10): 1167. CrossRef
Prevention and Treatment of Stricturing Crohn’s Disease – Perspectives and Challenges Joseph Sleiman, Sara El Ouali, Taha Qazi, Benjamin Cohen, Scott R. Steele, Mark E. Baker, Florian Rieder Expert Review of Gastroenterology & Hepatology.2021; 15(4): 401. CrossRef
Risk factors for rebleeding in Crohn's disease patients with acute severe lower gastrointestinal bleeding: With special reference to the role of anti‐tumor necrosis factor therapy Dae Sung Kim, Jiyoung Yoon, Ye‐Jee Kim, Jin Wook Lee, Seung Wook Hong, Ha Won Hwang, Sang Hyoung Park, Dong‐Hoon Yang, Byong Duk Ye, Jeong‐Sik Byeon, Seung‐Jae Myung, Suk‐Kyun Yang Journal of Gastroenterology and Hepatology.2021; 36(9): 2455. CrossRef
Crohn’s disease: a population-based study of surgery in the age of biological therapy Christian Stöss, Maximilian Berlet, Stefan Reischl, Ulrich Nitsche, Marie-Christin Weber, Helmut Friess, Dirk Wilhelm, Philipp-Alexander Neumann International Journal of Colorectal Disease.2021; 36(11): 2419. CrossRef
Novel mechanisms and clinical trial endpoints in intestinal fibrosis* Jie Wang, Sinan Lin, Jonathan Mark Brown, David van Wagoner, Claudio Fiocchi, Florian Rieder Immunological Reviews.2021; 302(1): 211. CrossRef
Is Paradigm for the Role of Balloon-Assisted Enteroscopy Changing in Crohn’s Disease? Yoo Jin Lee Gut and Liver.2021; 15(3): 325. CrossRef
Intestinal stricture in Crohn's disease: A 2020 update Xiao Xuan Lin, Yun Qiu, Xiao Jun Zhuang, Fen Liu, Xiao Min Wu, Min Hu Chen, Ren Mao Journal of Digestive Diseases.2021; 22(7): 390. CrossRef
Medical Management of Aggressive Inflammatory Bowel Disease: When Is the Time to Cut Your (and the Patient's) Losses? Jared Sninsky, Edward L. Barnes Journal of Laparoendoscopic & Advanced Surgical Techniques.2021; 31(8): 905. CrossRef
Epidemiology and diagnosis of inflammatory bowel diseases Kang-Moon Lee Journal of the Korean Medical Association.2021; 64(9): 579. CrossRef
Intestinal microbiota and inflammatory bowel diseases Chang Soo Eun Journal of the Korean Medical Association.2021; 64(9): 588. CrossRef
The Multiple Faces of Integrin–ECM Interactions in Inflammatory Bowel Disease Valentina Garlatti, Sara Lovisa, Silvio Danese, Stefania Vetrano International Journal of Molecular Sciences.2021; 22(19): 10439. CrossRef
A Novel Cause of Bowel Obstruction in a Patient with Long-Standing Crohn’s Disease Satya V. Vedula, T. Paul Nickerson, Douglas J. Grider, Mark Li cheng Wu Case Reports in Pathology.2021; 2021: 1. CrossRef
Background/Aims Intestinal fibrosis is a major complication of Crohn’s disease (CD). The profibrotic protein transforming growth factor-β (TGF-β) has been considered to be critical for the induction of the fibrotic program. TGF-β has the ability to induce not only the expression of extracellular matrix (ECM) including collagen, but also the production of plasminogen activator inhibitor-1 (PAI-1) that prevents enzymatic degradation of the ECM during the onset of fibrotic diseases. However, the significance of PAI-1 in the developing intestinal fibrosis has not been fully understood. In the present study, we examined the actual expression of PAI-1 in fibrotic legion of intestinal inflammation and its correlation with the abnormal ECM deposition.
Methods Chronic intestinal inflammation was induced in BALB/c mice using 8 repeated intrarectal injections of 2,4,6-trinitrobenzene sulfonic acid (TNBS). TM5275, a PAI-1 inhibitor, was orally administered as a carboxymethyl cellulose suspension each day for 2 weeks after the sixth TNBS injection.
Results Using a publicly available dataset (accession number, GSE75214) and TNBS-treated mice, we observed increases in PAI-1 transcripts at active fibrotic lesions in both patients with CD and mice with chronic intestinal inflammation. Oral administration of TM5275 immediately after the onset of intestinal fibrosis upregulated MMP-9 (matrix metalloproteinase 9) and decreased collagen accumulation, resulting in attenuation of the fibrogenesis in TNBS-treated mice.
Conclusions PAI-1-mediated fibrinolytic system facilitates collagen degradation suppression. Hence, PAI-1 inhibitor could be applied as an anti-fibrotic drug in CD treatment.
Citations
Citations to this article as recorded by
Novel Transcriptomic Signatures in Fibrostenotic Crohn’s Disease: Dysregulated Pathways, Promising Biomarkers, and Putative Therapeutic Targets Animesh Acharjee, Uday Shivaji, Giovanni Santacroce, Sarah Akiror, Louisa Jeffery, Csilla Varnai, Gary Reynolds, Davide Zardo, Snehali Majumder, Asma Amamou, Georgios V Gkoutos, Marietta Iacucci, Subrata Ghosh Inflammatory Bowel Diseases.2025; 31(6): 1502. CrossRef
The role of matrix metalloproteinase 9 in fibrosis diseases and its molecular mechanisms Yuling Wang, Linke Jiao, Caoxia Qiang, Chen Chen, Zihuan Shen, Fan Ding, Lifei Lv, Tingting Zhu, Yingdong Lu, Xiangning Cui Biomedicine & Pharmacotherapy.2024; 171: 116116. CrossRef
Plasminogen activator inhibitor-1 promotes immune evasion in tumors by facilitating the expression of programmed cell death-ligand 1 Abd Aziz Ibrahim, Taku Fujimura, Tomoko Uno, Tomoya Terada, Ken-ichi Hirano, Hiroyuki Hosokawa, Akio Ohta, Toshio Miyata, Kiyoshi Ando, Takashi Yahata Frontiers in Immunology.2024;[Epub] CrossRef
Fibrostenosing Crohn’s Disease: Pathogenetic Mechanisms and New Therapeutic Horizons Irene Mignini, Valentina Blasi, Fabrizio Termite, Giorgio Esposto, Raffaele Borriello, Lucrezia Laterza, Franco Scaldaferri, Maria Elena Ainora, Antonio Gasbarrini, Maria Assunta Zocco International Journal of Molecular Sciences.2024; 25(12): 6326. CrossRef
Impact of Plasminogen Activator Inhibitor-1 Serum Levels and the -675 4G/5G Variant in the SERPINE1 Gene on Systemic Sclerosis in a Mexican Population José Alvaro Lomelí-Nieto, José Francisco Muñoz-Valle, José Eduardo Navarro-Zarza, Christian Johana Baños-Hernández, Jesús Alberto Gutierrez-Brito, Valeria Renteria-Cabrera, Eduardo Arturo Horta-Chávez, José Javier Morales-Núñez, Samuel García-Arellano, Is Life.2024; 14(9): 1056. CrossRef
PAI-1 siRNA-loaded biomimetic nanoparticles for ameliorating diminished ovarian reserve and inhibiting ovarian fibrosis Hua Guo, Chang Xiao, Xinshu Li, Jialing Li, Xue Chen, Bin liu, Rong Hu European Journal of Pharmacology.2024; : 176948. CrossRef
Metformin acts on miR-181a-5p/PAI-1 axis in stem cells providing new strategies for improving age-related osteogenic differentiation decline Guanhao Hong, Yulan Zhou, Shukai Yang, Shouquan Yan, Jiaxu Lu, Bo Xu, Zeyu Zhan, Huasheng Jiang, Bo Wei, Jiafeng Wang Stem Cells.2024; 42(12): 1055. CrossRef
Phytochemical Compounds as Promising Therapeutics for Intestinal Fibrosis in Inflammatory Bowel Disease: A Critical Review Aya A. Touny, Balaji Venkataraman, Shreesh Ojha, Mauro Pessia, Veedamali S. Subramanian, Shamanth Neralagundi Hariharagowdru, Sandeep B. Subramanya Nutrients.2024; 16(21): 3633. CrossRef
Fibro-Stenosing Crohn’s Disease: What Is New and What Is Next? Virginia Solitano, Arianna Dal Buono, Roberto Gabbiadini, Marek Wozny, Alessandro Repici, Antonino Spinelli, Stefania Vetrano, Alessandro Armuzzi Journal of Clinical Medicine.2023; 12(9): 3052. CrossRef
Downregulation of Heat Shock Protein 72 Contributes to Fibrostenosis in Crohn’s Disease Seung Won Kim, Jae-Young Lee, Han Cheol Lee, Jae Bum Ahn, Ji Hyung Kim, I Seul Park, Jae Hee Cheon, Duk Hwan Kim Gut and Liver.2023; 17(6): 905. CrossRef
Revisiting fibrosis in inflammatory bowel disease: the gut thickens Silvia D’Alessio, Federica Ungaro, Daniele Noviello, Sara Lovisa, Laurent Peyrin-Biroulet, Silvio Danese Nature Reviews Gastroenterology & Hepatology.2022; 19(3): 169. CrossRef
The Molecular Mechanisms of Intestinal Inflammation and Fibrosis in Crohn’s Disease Yuki Hayashi, Hiroshi Nakase Frontiers in Physiology.2022;[Epub] CrossRef
Attenuation of Excess TNF-α Release in Crohn’s Disease by Silencing of iRHOMs 1/2 and the Restoration of TGF-β Mediated Immunosuppression Through Modulation of TACE Trafficking Taylor J. Louis, Ahmad Qasem, Saleh A. Naser Frontiers in Immunology.2022;[Epub] CrossRef
ZNF281 Promotes Colon Fibroblast Activation in TGFβ1-Induced Gut Fibrosis Ilaria Laudadio, Alex Bastianelli, Valerio Fulci, Claudia Carissimi, Eleonora Colantoni, Francesca Palone, Roberta Vitali, Elisa Lorefice, Salvatore Cucchiara, Anna Negroni, Laura Stronati International Journal of Molecular Sciences.2022; 23(18): 10261. CrossRef
Macrophages in intestinal fibrosis and regression Hui Yao, Guoyao Tang Cellular Immunology.2022; 381: 104614. CrossRef
Prevention and Treatment of Stricturing Crohn’s Disease – Perspectives and Challenges Joseph Sleiman, Sara El Ouali, Taha Qazi, Benjamin Cohen, Scott R. Steele, Mark E. Baker, Florian Rieder Expert Review of Gastroenterology & Hepatology.2021; 15(4): 401. CrossRef
Elevated expression of plasminogen activator inhibitor (PAI-1/SERPINE1) is independent from rs1799889 genotypes in arthrofibrosis Banu Bayram, Aaron R. Owen, Amel Dudakovic, Jacob W. Bettencourt, Afton K. Limberg, Mark E. Morrey, Joaquin Sanchez-Sotelo, Daniel J. Berry, Jean-Pierre A. Kocher, Andre J. van Wijnen, Matthew P. Abdel Meta Gene.2021; 28: 100877. CrossRef
Molecular targets and the use of biologics in the management of small bowel fibrosis in inflammatory bowel disease Muaad Abdulla, Thean Soon Chew Current Opinion in Gastroenterology.2021; 37(3): 275. CrossRef
Intestinal stricture in Crohn's disease: A 2020 update Xiao Xuan Lin, Yun Qiu, Xiao Jun Zhuang, Fen Liu, Xiao Min Wu, Min Hu Chen, Ren Mao Journal of Digestive Diseases.2021; 22(7): 390. CrossRef
Therapeutic applications of PAI-1 inhibitor for the treatment of hematological malignancies Takashi Yahata Japanese Journal of Thrombosis and Hemostasis.2020; 31(3): 310. CrossRef