Fousekis Fotios S, Mpakogiannis Konstantinos, Mastorogianni Ioanna Nefeli, Lianos Georgios D, Christodoulou Dimitrios K, Katsanos Konstantinos H
Department of Gastroenterology and Hepatology, University Hospital of Ioannina, University of Ioannina, 45110 Ioannina, Greece.
Department of Surgery, University Hospital of Ioannina, 45110 Ioannina, Greece.
J Clin Med. 2025 Jun 8;14(12):4060. doi: 10.3390/jcm14124060.
Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that often leads to intestinal fibrosis, an irreversible complication associated with strictures and the need for surgical intervention. Fibrosis occurs due to prolonged inflammation and abnormal wound healing, involving complex interactions between immune cells, mesenchymal cells, cytokines, and the gut microbiota. Key fibrogenic mechanisms include the activation of fibroblasts and myofibroblasts, cytokine signaling, and disrupted turnover of the extracellular matrix. Advancements in imaging techniques, such as MRI and CT enterography, have improved the detection and monitoring of fibrosis. Additionally, molecular techniques targeting fibroblast activation proteins show promise as a new imaging method. However, there are currently no approved anti-fibrotic therapies for CD. Emerging strategies focus on key pathways and novel therapeutic targets, including growth factor modulators, intracellular enzyme and kinases modulators, and interventions targeting the modulation of inflammation and extracellular matrix, which are being evaluated in preclinical and clinical settings. This review discusses the pathophysiology, diagnostic advancements, and therapeutic perspectives related to intestinal fibrosis in CD, emphasizing the urgent need for targeted anti-fibrotic therapies to prevent long-term complications and improve the life quality of patients.
克罗恩病（CD）是一种胃肠道慢性炎症性疾病，常导致肠道纤维化，这是一种与狭窄及手术干预需求相关的不可逆并发症。纤维化是由于长期炎症和异常伤口愈合所致，涉及免疫细胞、间充质细胞、细胞因子和肠道微生物群之间的复杂相互作用。关键的纤维化机制包括成纤维细胞和平滑肌肌动蛋白阳性成纤维细胞的激活、细胞因子信号传导以及细胞外基质周转的破坏。成像技术的进步，如磁共振成像（MRI）和CT小肠造影，改善了对纤维化的检测和监测。此外，靶向成纤维细胞激活蛋白的分子技术有望成为一种新的成像方法。然而，目前尚无获批用于治疗CD的抗纤维化疗法。新兴策略聚焦于关键途径和新的治疗靶点，包括生长因子调节剂、细胞内酶和激酶调节剂，以及针对炎症和细胞外基质调节的干预措施，这些正在临床前和临床环境中进行评估。本综述讨论了与CD肠道纤维化相关的病理生理学、诊断进展和治疗前景，强调迫切需要有针对性的抗纤维化疗法，以预防长期并发症并提高患者生活质量。
