Role of ZNF281 in intestinal fibroblast activation: new insights in IBD-related fibrosis

Serious complications of Crohn’s disease (CD), a form of Inflammatory Bowel Disease (IBD), involve the formation of intestinal fibrotic stenosis followed by obstruction. Chronic inflammatory state activates resident fibroblasts and myofibroblasts, that are the key effector cells in fibrosis, being responsible for the synthesis of ECM proteins. Exposure of human colon fibroblasts (CCD18-Co) to the pro-fibrotic cytokine TGF-β1 is sufficient to induce the expression of genes associated with myofibroblast features such as cell migration, ECM remodeling and contraction. Furthermore, during TGFβ1-mediated myofibroblast differentiation, the transcription factor ZNF281 is increased and is required to reshape the expression of genes encoding for myofibroblast markers, suggesting an active role for ZNF281 as a master regulator of intestinal myofibroblast functions. 12 samples