Wnt activator FOXQ1 drives intestinal fibrosis in inflammatory bowel diseases

Intestinal fibrosis is a serious complication of inflammatory bowel diseases (IBD).

There are currently no treatment options for fibrotic tissue scarring other than surgical interventions, which severely impact the affected persons´ quality of life.

Epithelial-mesenchymal transition (EMT) of intestinal epithelia contributes to tissue fibrosis, but the mechanisms that drive EMT in IBD remain incompletely understood.Our studies suggest that intestinal inflammation triggers the expression of the forkhead box family transcription factor FOXQ1, which is a well-known mediator of EMT in various types of cancer, and a potent activator of pro-fibrotic β-catenin signaling.

Thus, we have reason to believe that FOXQ1 links inflammatory signaling to β-catenin-dependent EMT in IBD.

We will therefore comprehensively explore the pathophysiological role of FOXQ1 in IBD, using classic as well as state-of-the-art molecular biology techniques in human tissue samples and model cell lines.

In particular, we intend to address i) how FOXQ1 is induced in intestinal inflammation, ii) which genes are under FOXQ1 control in the inflamed intestine, and iii) by which molecular mechanisms FOXQ1 contributes to inflammation-associated fibrosis.We believe that unravelling the biology of FOXQ1 in IBD will uncover therapeutic vulnerabilities for preventing tissue scarring during inflammation.

Moreover, these discoveries may also be relevant for EMT and metastasis in cancer.