Kalafateli Maria, Tourkochristou Evanthia, Tsounis Efthymios P, Aggeletopoulou Ioanna, Triantos Christos
Department of Gastroenterology, General Hospital of Patras, Patras, Greece.
Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece.
Inflamm Bowel Dis. 2025 Feb 10;31(2):579-592. doi: 10.1093/ibd/izae292.
Strictures in inflammatory bowel disease, especially Crohn's disease (CD), are characterized by increased intestinal wall thickness, which, according to recent accumulating data, is mainly attributed to the expansion of the intestinal smooth muscle layers and to a lesser extent to collagen deposition. In this review, we will discuss the role of intestinal smooth muscle cells (SMCs) as crucial orchestrators of stricture formation. Activated SMCs can synthesize extracellular matrix (ECM), thus contributing to intestinal fibrosis, as well as growth factors and cytokines that can further enhance ECM production, stimulate other surrounding mesenchymal and immune cells, and increase SMC proliferation via paracrine or autocrine signaling. There is also evidence that, in stricturing CD, a phenotypic modulation of SMC toward a myofibroblast-like synthetic phenotype takes place. Moreover, the molecular mechanisms and signaling pathways that regulate SMC hyperplasia/hypertrophy will be extensively reviewed. The understanding of the cellular network and the molecular background behind stricture formation is essential for the design of effective anti-fibrotic strategies, and SMCs might be a promising therapeutic target in the future.
炎症性肠病，尤其是克罗恩病（CD）中的狭窄，其特征为肠壁厚度增加。根据最近积累的数据，这主要归因于肠道平滑肌层的扩张，其次是胶原沉积。在本综述中，我们将讨论肠道平滑肌细胞（SMC）作为狭窄形成的关键协调者的作用。活化的SMC可合成细胞外基质（ECM），从而导致肠道纤维化，还可合成生长因子和细胞因子，这些因子可进一步增强ECM的产生，刺激其他周围的间充质和免疫细胞，并通过旁分泌或自分泌信号增加SMC增殖。也有证据表明，在狭窄性CD中，SMC会向肌成纤维细胞样合成表型发生表型调节。此外，还将广泛综述调节SMC增生/肥大的分子机制和信号通路。了解狭窄形成背后的细胞网络和分子背景对于设计有效的抗纤维化策略至关重要，并且SMC未来可能是一个有前景的治疗靶点。
