CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy.
Int J Mol Sci. 2024 Jun 7;25(12):6326. doi: 10.3390/ijms25126326.
Bowel strictures are well recognized as one of the most severe complications in Crohn's disease, with variable impacts on the prognosis and often needing surgical or endoscopic treatment. Distinguishing inflammatory strictures from fibrotic ones is of primary importance due to the different therapeutic approaches required. Indeed, to better understand the pathogenesis of fibrosis, it is crucial to investigate molecular processes involving genetic factors, cytokines, alteration of the intestinal barrier, and epithelial and endothelial damage, leading to an increase in extracellular matrix synthesis, which ultimately ends in fibrosis. In such a complex mechanism, the gut microbiota also seems to play a role. A better comprehension of molecular processes underlying bowel fibrosis, in addition to radiological and histopathological findings, has led to the identification of high-risk patients for personalized follow-up and testing of new therapies, primarily in preclinical models, targeting specific pathways involving Transforming Growth Factor-β, interleukins, extracellular matrix balance, and gut microbiota. Our review aims to summarize current evidence about molecular factors involved in intestinal fibrosis' pathogenesis, paving the way for potential diagnostic biomarkers or anti-fibrotic treatments for stricturing Crohn's disease.
肠狭窄是克罗恩病最严重的并发症之一，对预后有不同的影响，常需要手术或内镜治疗。由于所需的治疗方法不同，区分炎症性狭窄和纤维性狭窄至关重要。事实上，为了更好地了解纤维化的发病机制，必须研究涉及遗传因素、细胞因子、肠道屏障改变以及上皮和内皮损伤的分子过程，这些过程导致细胞外基质合成增加，最终导致纤维化。在这种复杂的机制中，肠道微生物群似乎也发挥了作用。除了放射学和组织病理学发现外，对肠纤维化发病机制中分子过程的更好理解，导致了对高风险患者进行个性化随访和新疗法测试的识别，主要是在临床前模型中，针对涉及转化生长因子-β、白细胞介素、细胞外基质平衡和肠道微生物群的特定途径。我们的综述旨在总结目前关于参与肠道纤维化发病机制的分子因素的证据，为诊断标志物或抗纤维化治疗狭窄性克罗恩病铺平道路。
