Fibroblast growth factors in epithelial repair and cytoprotection

Susanne Braun, Ulrich auf dem Keller, Heike Steiling, Sabine Werner

Abstract

Growth factors are polypeptides that stimulate the division of certain cell types at low concentrations. Fibroblast growth factor (FGF) 7 (FGF–7) and its homologue FGF–10 act specifically on various types of epithelial cells including keratinocytes of the skin, intestinal epithelial cells and hepatocytes. In addition, FGF–7 and FGF–10 have been shown to be more than growth factors: they can protect epithelial cells from damaging effects induced, for example, by radiation and oxidative stress. Therefore, they are currently in clinical trials for the treatment of oral mucositis, a severe side–effect of cancer therapy characterized by painful inflammation and ulceration of the oral epithelium. To gain insight into the mechanisms of FGF–7/FGF–10 action in epithelial cells, we searched for genes that are regulated by these growth factors. Indeed, we identified genes that help us to explain the mechanisms that underlie the effects of FGF–7. Most interestingly, several genes were identified that are likely to mediate the cytoprotective effect of FGF–7 for epithelial cells in vitro and possibly also in injured and diseased tissues in vivo.