The Role of Scleraxis in Intestinal Fibroblasts

Abstract

Scleraxis is a transcription factor in the BHLH family originally shown to regulate the development of embryonic tissue into tendon and bone—suggesting a link to collagen production and release. Recently, scleraxis has been shown to play a role in the development cardiac fibrosis. Organ fibrosis typically follows inflammation and involves over activation of myofibroblasts (activated fibroblasts that express α‐smooth muscle actin). Intestinal fibrosis is a somewhat common complication of Inflammatory Bowel Disease (IBD), which primarily includes Crohn's Disease (CD) and Ulcerative Colitis (UC). Intestinal fibrosis is characterized by dysregulated and excessive production of collagen from fibroblasts that results in excessive contraction in the intestine, intestinal stricture and bowel obstruction. Interestingly, approximately 20–25% of IBD patients will develop fibrosis. We hypothesize that scleraxis is expressed by intestinal fibroblasts and can modify the activation of such fibroblasts. Transfection (siRNA) studies show that when scleraxis is reduced in fibroblasts there is an increase in intestinal fibroblast attachment to fibrinogen (CD11b ligand). While exposure of fibroblasts to cytokines does not appear to regulate its expression, scleraxis expression is increased in IBD intestines. Immuno‐purification studies reveal that scleraxis may have a physical link to CD11b suggesting that they may have similar signaling pathways. These results highlight scleraxis as a target molecule in the treatment of diseases involving the over‐activation of fibroblasts.Support or Funding Information5T35DK007431‐32 and and National Science Foundation RII