KERATINOCYTE GROWTH-FACTOR IS AN IMPORTANT ENDOGENOUS MEDIATOR OF HAIR FOLLICLE GROWTH, DEVELOPMENT, AND DIFFERENTIATION - NORMALIZATION OFTHE NU NU FOLLICULAR DIFFERENTIATION DEFECT AND AMELIORATION OF CHEMOTHERAPY-INDUCED ALOPECIA/

The growth and development of hair follicles is influenced by a number of different growth factors and cytokines, particularly members of th e fibroblast growth factor (FGF) family, Keratinocyte growth factor (K GF or FGF-7) is a recently identified 28-kd member of the FGF family t hat induces proliferation of a wide variety of epithelial cells, inclu ding keratinocytes within the epidermis and dermal adnexa. Because KGF induces marked proliferation of keratinocytes, and both KGF and KGF r eceptor (KGFR) mRNA are expressed at high levels in skin, we sought to localize KGF and KGFR in skin by in situ hybridization KGFR mRNA was relatively strongly expressed by keratinocytes in the basilar epidermi s as well as throughout developing hair follicles of rat embryos and n eonates, KGF mRNA was expressed at lower levels than was KGFR but coul d be localized to follicular dermal papillae in rat embryos and neonat es. These results prompted us to investigate the effects of KGF on hai r follicles in two distinct murine models of alopecia. In the first mo del, recombinant KGF (rKGF) induced dose-dependent hair growth over mo st of the body in nu/nu athymic nude mice when administered intraperit oneally or subcutaneously over 17 to 18 days. When administered subcut aneously, rKGF induced the most extensive hair growth at the sites of injection. Histologically, rKGF induced marked follicular and sebaceou s gland hypertrophy, a normalization of the nu/nu follicular keratiniz ation defect, and an increase in follicular keratinocyte proliferation as assessed by bromodeoxyuridine labeling. In the second model, a neo natal mt model of cytosine arabinoside chemotherapy-induced alopecia i n which interleukin-1, epidermal growth factor, and acidic FGF have al l demonstrated some degree of alopecia cytoprotective, rKGF induced a dose-dependent cytoprotective effect, abrogating as much as 50% of the alopecia in this model when administered beginning I day before the o nset of chemotherapy. Taken together these data suggest that KGF is an important endogenous mediator of normal hair follicle growth, develop ment, and differentiation.