Involvement of hepatocyte growth factor/scatter factor and Met receptor signaling in hair follicle morphogenesis and cycling

HGF/SF and its receptor (Met) are principal mediators of mesenchymal-epithe lial interactions in several different systems and have recently been impli cated in the control of hair follicle (HF) growth, We have studied their ex pression patterns during HF morphogenesis and cycling in C57BL/6 mice, wher eas functional hair growth effects of HGF/SF were assessed in vivo by analy sis of transgenic mice and in skin organ culture. In normal mouse skin, fol licular expression of HGF/SF and Met was strikingly localized: HGF/SF was f ound only in the HF mesenchyme (dermal papilla fibroblasts) and Met in the neighboring hair bulb keratinocytes, Both HGF/SF and Met expression peaked during the initial phases of HF morphogenesis, the stage of active hair gro wth (early and mid anagen), and during the apoptosis-driven HF regression ( catagen), Met+ cells in the regressing epithelial strand appeared to be pro tected from undergoing apoptosis. Compared to wild-type controls, transgeni c mice overexpressing HGF/SF under the control of the MT-I promoter had twi ce as many developing HF and displayed accelerated HF development on postna tal day 3, They also showed significant catagen retardation on P17, In orga n culture and in vivo, HGF/SF i.c. resulted in a significant catagen retard ation. These results demonstrate an important role of HGF/SF and Met in mur ine hair growth control and suggest that Met-mediated signaling might be ex ploited for therapeutic manipulation of human hair growth disorders.-Lindne r, G., Menrad, A., Gherardi, E., Merlino, G,, Welker, P., Handjiski, B., Ro loff, B,, Paus, R. Involvement of hepatocyte growth factor/scatter factor a nd Met receptor signaling in hair follicle morphogenesis and cycling.