Creeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn's disease strictures.

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.

SUBMITTER: Bauer-Rowe KE 

PROVIDER: S-EPMC12453597 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature