In androgenetic alopecia androgens inhibit scalp hair follicles eventually causing balding. Androgens probably act by altering paracrine regulatory factors produced by the dermal papilla. Since hepatocyte growth factor (HGF) family members, HGF and macrophage stimulating protein (MSP), are implicated in hair growth, they seem possible candidates for roles as androgen-regulated paracrine factors. This study was designed to investigate whether, and where, these genes were expressed in human hair follicles and whether balding altered their expression.
Scalp skin from healthy individuals was transported in RNA stabilization reagent, RNAlater, for RT-PCR and media for cell culture. Individually microdissected hair follicles (n=5) expressed genes for MSP and its receptor, RON, and HGF and its receptor, c-Met. Sequencing confirmed gene identity. When bulb components were isolated separately (n=3), the dermal papilla and dermal sheath expressed MSP, RON, HGF, and c-Met, while the bulb matrix expressed only MSP and RON. Cultured scalp dermal papilla cells also expressed MSP, RON, HGF and c-Met. In balding follicles (n=3) no MSP was detected; real-time (quantitative) PCR revealed lower level of HGF and c-Met in isolated balding hair follicles. Balding cultured dermal papilla cells expressed only low levels of HGF (n=5).
Thus, human hair follicles express the genes and receptors for 2 HGF family members. The expression of both paracrine factors and their receptors by normal dermal papilla and sheath, while the epithelial bulb matrix cells only produce MSP and RON, suggests an autocrine dermal papilla role for HGF; MSP appears to act on both papilla and matrix. Since balding follicles and dermal papilla cells express less MSP and HGF, these paracrine factors are probably involved in producing large hair follicles. Therefore, drugs which increase the levels of these factors could stimulate better hair growth in alopecia.