Lovisa Sara, Vetrano Stefania
Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, Milan, Italy.
Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy.
Heliyon. 2024 Nov 24;10(23):e40604. doi: 10.1016/j.heliyon.2024.e40604. eCollection 2024 Dec 15.
Fibrosis is the pathological consequence of chronic inflammation. In Crohn's disease (CD), fibrostenotic complications occur with 50-70 % frequency as a failure to properly repair the tissue damage. Intestinal stenosis requires surgical intervention and relapses in most patients. Mesenchymal cells encompassed of heterogeneous cell subsets orchestrate this complex process. The lack of a full characterization of the stromal diversity and function in CD has consequently slowed the development of anti-fibrotic targets. Two recent studies align together demonstrating FAPTWIST1 fibroblasts as the primary mesenchymal population driving intestinal fibrosis in CD. Genetic and pharmacological targeting of Twist1 in mouse models proved the functional role of FapTwist1 fibroblasts and indicate the use of the Twist1 inhibitor harmine as a potential therapeutic strategy to revert fibrosis.
纤维化是慢性炎症的病理后果。在克罗恩病(CD)中,50%-70%的患者会出现纤维狭窄并发症,这是组织损伤未能得到适当修复的结果。肠道狭窄需要手术干预,且大多数患者会复发。由异质性细胞亚群组成的间充质细胞协调这一复杂过程。由于缺乏对CD中基质多样性和功能的全面表征,抗纤维化靶点的开发因此受到了阻碍。最近的两项研究一致表明,FAPTWIST1成纤维细胞是驱动CD肠道纤维化的主要间充质细胞群。在小鼠模型中对Twist1进行基因和药物靶向研究,证明了FapTwist1成纤维细胞的功能作用,并表明使用Twist1抑制剂harmine作为逆转纤维化的潜在治疗策略。