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.

Adenosine stimulates growth of dermal papilla and lengthens the anagen phase by increasing the cysteine level via fibroblast growth factors 2 and 7 in an organ culture of mouse vibrissae hair follicles

“…It stimulates VEGF production through activation of cell surface adenosine receptors, and this adenosine-mediated signal transduction pathway contributes to minoxidil-induced hair growth (9). Gene expression of FGF-7 was up-regulated by adenosine treatment in DP cells (10). Oura et al (17) demonstrated that adenosine significantly increased the anagen hair growth rate and the thickness of hair in a human clinical study.…”

“…Li et al (9) proposed an adenosine mediated mechanism for minoxidil-induced vascular endothelial growth factor (VEGF) production by the signaling pathway. Iino et al (10) reported that adenosine stimulates FGF-7 gene expression. However, the potential effects of adenosine on hair growth have not been fully elucidated.…”

In <i>Vitro</i> Effects of the Phytocomplex TrichoTech<sup>TM</sup> on Human Fibroblasts: Proliferative Potential and Effects on Gene Expression of FGF-7 and FGF-10

“…Among these FGF genes, FGF-7 was found to be expressed in the hair follicle. FGF-7 RNA is localized to the dermal papilla during anagen, but expression is down-regulated by the lateanagen VI stage [22]. Besides, no FGF-7 RNA was detected in follicles during catagen or telogen [23].…”

Recent improvements in the development of A2B adenosine receptor agonists

“…Studies performed by the Shiseido Research Group indicate that adenosine, via A 2B AR, might stimulate hair growth through fibroblast growth factor-7 gene expression upregulation in dermal papilla cells [57].…”