Intestinal growth factors: potential use in the treatment of inflammatory bowel disease and their role in mucosal healing

Abstract

Background: A key feature of inflammatory bowel disease (IBD) is impaired epithelial repair. Human growth factors comprise an array of signaling molecules that lead to ligand-specific signal transduction. Their downstream effects are associated with several cellular functions including epithelial healing in response to injury. Several studies have described specific growth factor deficiencies in patients with IBD, implicating their role in disease pathophysiology. The aim of this review was to describe currently known enterocyte-targeted growth factors, their mechanisms of action, and their potential therapeutic utility.

Methods: The National Library of Medicine (http://www.pubmed.gov) and meeting abstracts were searched using the following terms: growth factor, intestine, colon, inflammatory bowel disease, Crohn's disease, ulcerative colitis, colitis, animal model, transforming growth factor, bone morphogenetic protein, activins, growth hormone, fibroblast growth factor, epidermal growth factor (EGF), keratinocyte growth factor (KGF), glucagon-like peptide II, granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), vascular endothelial growth factor (VEGF) inhibitors, and trefoil factors.

Results: Several growth factors are therapeutic candidates in IBD. Growth hormone, KGF, EGF, teduglutide, GM-CSF/G-CSF have entered early clinical trials, whereas others are currently in preclinical evaluation.

Conclusions: There are several growth factors responsible for epithelial repair. Preliminary studies using recombinant growth factors seem promising in IBD preclinical and clinical trials.