Connective tissue growth factor: a novel regulator of mucosal repair and fibrosis in inflammatory bowel disease?

Abstract

Inflammatory bowel disease (IBD) is a multifactorial disorder which is characterized by massive damage of the epithelium and the underlying mesenchyme of the intestine. Due to the potent effect of connective tissue growth factor (CTGF) on fibroblast proliferation and connective tissue deposition we speculated about a possible role of this mitogen in IBD. Here we demonstrate a strikingly increased expression of CTGF mRNA in surgical specimens of patients suffering from two forms of IBD, Crohn's disease and ulcerative colitis. In most specimens, the levels of CTGF mRNA correlated with the degree of inflammation as assessed by histological analysis of adjacent tissue samples and by expression analysis of the pro-inflammatory cytokine interleukin-1 beta. However, areas of little inflammation which were characterized by severe fibrosis also revealed high levels of CTGF mRNA. Expression of transforming growth factor beta-1 (TGF-beta 1), the only known inducer of CTGF so far, as well as of the CTGF target genes collagen I alpha 1, fibronectin and integrin alpha 5 revealed a strong correlation with the expression of CTGF. These data suggest a prominent role of CTGF in the repair of mucosal injury in IBD and in the aberrant deposition of extracellular matrix leading to fibrosis and stenosis, one major complication in IBD, especially in Crohn's disease.