Keratinocyte growth factor protects epidermis and hair follicles from cell death induced by UV irradiation, chemotherapeutic or cytotoxic agents.
Owing to its potent cytoprotective properties for epithelial cells, keratinocyte growth factor (KGF) is successfully used for the treatment of chemotherapy- and radiotherapy-induced oral mucositis in cancer patients. It is therefore of major interest to determine possible clinical applications of KGF in other organs and in different stress situations and to unravel common and organ-specific mechanisms of KGF action. Here we show that KGF protects human keratinocytes from the toxicity of xenobiotics with electrophilic and oxidative properties and reduces the cell death induced by UV irradiation. In contrast to other cell types, cytoprotection of keratinocytes by KGF is not a direct anti-apoptotic effect but requires de novo protein synthesis. The in vitro findings are clinically relevant because KGF protected keratinocytes in organ-cultured human scalp hair follicles from the toxicity of the xenobiotic menadione. Moreover, injection of KGF into murine back skin markedly reduced cell death in the epidermis after UVB irradiation. This activity is dependent on FGF receptor signaling because it was abrogated in transgenic mice expressing a dominant-negative FGF receptor mutant in keratinocytes. Taken together, our results encourage the use of KGF for skin protection from chemical and physical insults.
Braun
Susanne
S
Institute of Cell Biology, Department of Biology, ETH Zurich, Honggerberg, 8093 Zurich, Switzerland.
Krampert
Monika
M
Bodó
Enikö
E
Kümin
Angelika
A
Born-Berclaz
Christiane
C
Paus
Ralf
R
Werner
Sabine
S
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects*; D003603:Cytotoxins / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions; D004817:Epidermis / Q000187:drug effects* / Q000528:radiation effects*; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology*; D018859:Hair Follicle / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D014176:Protein Biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014466:Ultraviolet Rays / Q000009:adverse effects
D003603:Cytotoxins; D017382:Reactive Oxygen Species; D051523:Fibroblast Growth Factor 7