Lenti Marco Vincenzo, Santacroce Giovanni, Broglio Giacomo, Rossi Carlo Maria, Di Sabatino Antonio
Department of Internal Medicine and Medical Therapeutics, University of Pavia, First Department of Internal Medicine, San Matteo Hospital Foundation, Pavia, Italy.
Department of Internal Medicine and Medical Therapeutics, University of Pavia, First Department of Internal Medicine, San Matteo Hospital Foundation, Pavia, Italy.
Mol Aspects Med. 2024 Apr;96:101251. doi: 10.1016/j.mam.2024.101251. Epub 2024 Feb 14.
Despite many progresses have been made in the treatment of inflammatory bowel disease, especially due to the increasing number of effective therapies, the development of tissue fibrosis is a very common occurrence along the natural history of this condition. To a certain extent, fibrogenesis is a physiological and necessary process in all those conditions characterised by chronic inflammation. However, the excessive deposition of extracellular matrix within the bowel wall will end up in the formation of strictures, with the consequent need for surgery. A number of mechanisms have been described in this process, but some of them are not yet clear. For sure, the main trigger is the presence of a persistent inflammatory status within the mucosa, which in turn favours the occurrence of a pro-fibrogenic environment. Among the main key players, myofibroblasts, fibroblasts, immune cells, growth factors and cytokines must be mentioned. Although there are no available therapies able to target fibrosis, the only way to prevent it is by controlling inflammation. In this review, we summarize the state of art of the mechanisms involved in gut fibrogenesis, how to diagnose it, and which potential targets could be druggable to tackle fibrosis.
尽管在炎症性肠病的治疗方面已经取得了许多进展,特别是由于有效治疗方法的数量不断增加,但在这种疾病的自然病程中,组织纤维化的发展是一种非常常见的现象。在一定程度上,纤维化形成是所有以慢性炎症为特征的疾病中的一个生理且必要的过程。然而,肠壁内细胞外基质的过度沉积最终会导致狭窄的形成,从而需要进行手术。在这个过程中已经描述了许多机制,但其中一些尚不清楚。可以肯定的是,主要触发因素是黏膜内持续存在的炎症状态,这反过来又有利于促纤维化环境的出现。在主要的关键因素中,必须提到肌成纤维细胞、成纤维细胞、免疫细胞、生长因子和细胞因子。尽管目前没有能够针对纤维化的治疗方法,但预防纤维化的唯一方法是控制炎症。在这篇综述中,我们总结了肠道纤维化形成所涉及机制的现状、如何诊断它以及哪些潜在靶点可以作为治疗纤维化的药物靶点。