The Involvement of Glial Cell-Derived Neurotrophic Factor in Inflammatory Bowel Disease

Inflammatory bowel diseases (IBD) are chronic inflammatory gastrointestinal diseases characterized by dysregulation of the intestinal epithelial barrier (IEB) and intermittent relapses. Recent data show that the glial cell line-derived neurotrophic factor (GDNF) promotes IEB function and wound healing. Apart from protective effects of GDNF on enteric nervous system and IEB, an immunomodulatory role has been assumed. However, it is inconsistent whether GDNF levels are increased or decreased in the inflamed colon of patients with IBD. Furthermore, GDNF is 1 of 3 protein markers associated with relapse in a prospective cohort study in IBD patients with clinically and endoscopically quiescent disease. Additionally, not only enteric glial cells (EGCs), but also intestinal smooth muscle cells and enterocytes synthesize GDNF in significant amounts; in addition, its receptors are expressed in intestinal neurons, EGCs, immune cells and epithelial cells, which points to a potential auto- or paracrine signaling loop between some of these cells. Whether GDNF is involved in IBD-associated fibrosis and colitis-associated colorectal cancer remains to be confirmed. In this review we aim to summarize and discuss the current knowledge on the effects of GDNF and its potential role in the contribution to the pathogenesis of IBD.