Adenosine Stimulates Fibroblast Growth Factor-7 Gene Expression Via Adenosine A2b Receptor Signaling in Dermal Papilla Cells

Abstract

It has been previously reported that an adenosine receptor-mediated signal-transduction pathway in the dermal papilla cells (DPCs) of hair contributes to minoxidil-induced hair growth. In this study, we investigated this hypothesis further and have elucidated some underlying mechanisms. We performed DNA microarray analyses of DPCs and found that adenosine stimulation increases fibroblast growth factor-7 (FGF-7) gene expression levels by greater than 2-fold. Elevations of the extracellular FGF-7 protein levels were also observed. These upregulations of FGF-7 both at mRNA and protein levels were inhibited by A2b adenosine receptor-specific antagonist, alloxazine, but not by antagonists for other subtypes. In addition, the intracellular cAMP levels were raised by adenosine in a dose-dependent manner. Moreover, an increase of intracellular cAMP augmented the FGF-7 upregulation. Taken together, these results show that adenosine treatment of DPCs upregulates FGF-7 expression via the A2b adenosine receptor and that cAMP acts as one of the second messengers in this pathway. Furthermore, treatment with FGF-7 at concentrations of 10 ng/ml or greater significantly stimulated hair fiber elongation in human scalp hair follicle organ cultures. These data imply that adenosine might stimulate hair growth through FGF-7 upregulation in DPCs.