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

Creeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn's disease strictures. Cell Bauer-Rowe, K. E., Pham, B., Griffin, M., Liang, N. E., Kim, A., Lu, J. M., Januszyk, M., Guo, J. L., De Santis, S., Xing, Y., Prystupa, A., Sidhu, I., Suh, E. J., Foster, D. S., Korah, M., Goyal, A., Wan, D. C., Norton, J. A., Delitto, D., Pizarro, T. T., Naik, S. L., Hyun, J. S., Longaker, M. T. 2025

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.

View details for DOI 10.1016/j.cell.2025.08.029

View details for PubMedID 40967215