爬行脂肪来源的机械敏感成纤维细胞驱动克罗恩病狭窄的肠道纤维化，这一成果由斯坦福大学医学院Michael T. Longaker课题组经过不懈努力而取得。相关论文于2025年9月17日发表在《细胞》杂志上。
通过构建人类单细胞CD成纤维细胞图谱，课题组人员鉴定了CF衍生的CTHRC1+成纤维细胞，这些成纤维细胞富含yes相关蛋白(YAP)/具有pdz结合基序（TAZ）特征的转录共激活因子，并定位于狭窄的纤维化CF-肠壁界面。课题组研究人员进一步发现，在肠纤维化的小鼠模型中，类似的Cthrc1+ 小鼠成纤维细胞来源于肠系膜脂肪组织基质细胞，浸润纤维化肠，并以YAP/TAZ依赖的方式沉积细胞外基质。他们的发现确定了CF是促纤维化成纤维细胞的关键来源，并提出了通过不仅针对肠道而且针对CF来改善未来狭窄进展的临床管理的可能性。
研究人员表示，克罗恩病（CD）的一个重要并发症是肠纤维化，它使肠管变窄形成狭窄。蠕动脂肪（CF）是病变肠周围肠系膜脂肪组织的包裹物，其在CD狭窄进展中的作用尚不清楚。
附：英文原文
Title: Creeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn’s disease strictures
Author: Khristian E. Bauer-Rowe, Benjamin Pham, Michelle Griffin, Norah E. Liang, Alexia Kim, John M. Lu, Michael Januszyk, Jason L. Guo, Stefania De Santis, Yue Xing, Aleksandr Prystupa, Ikjot Sidhu, Elijah J. Suh, Deshka S. Foster, Maria Korah, Alka Goyal, Derrick C. Wan, Jeffrey A. Norton, Daniel Delitto, Theresa T. Pizarro, Shruti L. Naik, Jeong S. Hyun, Michael T. Longaker
Issue&Volume: 2025-09-17
Abstract: A significant complication of Crohn’s disease (CD) is intestinal fibrosis, which narrows the bowel lumen to form a stricture. Creeping fat (CF) is the wrapping of mesenteric adipose tissue around diseased bowel, of which the role in CD stricture progression is unclear. By constructing a human single-cell CD fibroblast atlas, we identified CF-derived, CTHRC1+ fibroblasts enriched for Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signatures and localized to a fibrotic CF-bowel wall interface within the stricture. We further showed that analogous Cthrc1+ mouse fibroblasts derive from mesenteric adipose tissue stromal cells, infiltrate fibrotic bowel, and deposit extracellular matrix in a YAP/TAZ-dependent manner in a mouse model of intestinal fibrosis. Our findings identify CF as a key source of pro-fibrotic fibroblasts and raise the possibility of improving future clinical management of stricture progression by targeting not only the bowel but also CF.
DOI: 10.1016/j.cell.2025.08.029
Source: https://www.cell.com/cell/abstract/S0092-8674(25)01018-9