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Hair regression and balding are distressing concerns for an increasing numberof people due to changes in lifestyle and serious nutritional imbalances. Therapiesfor treatment of hair loss are needed. Among potential therapeutics, adenosinehas been suggested as a potent regulator of hair growth. In this study, we investigatedthe effects of adenosine on hair follicles and dermal papilla (DP) cells, andthe mechanism underlying the action of adenosine. Hair follicles are organs, includingDP cells, that are responsible for the production of hair fibers by inducing andmaintaining the hair growth phase (anagen). In a culture of DP cells in vitro,adenosine stimulated proliferation of DP cells by increasing thymidine uptake.Subsequently, adenosine activated and elongated the anagen phase by increasingthe uptake of radiolabeled cysteine in an organ culture of mouse vibrissae hairfollicles. We also confirmed that adenosine promoted the expression of severalgrowth factors that are responsible for hair growth, including fibroblast growthfactors (FGF)-7, FGF-2, insulin-like growth factor (IGF)-1, and vascular endothelialgrowth factor (VEGF) in a cDNA microarray with semi-quantitative RT-PCR. Transcriptionalactivation of β-catenin in DP cells was increased by adenosine in a luciferaseassay. β-catenin is a co-activator of Wnt/β-catenin signaling that induces morphogenesisand differentiation of hair follicles and also acts to transactivate downstreamsignaling pathways, including the ERK pathway. Using Western blotting, we foundthat adenosine stimulated phosphorylation of ERK, CREB and AKT. These resultssuggest that adenosine stimulates growth of hair follicles by triggering the expressionof growth factors and β-catenin, and by inducing their downstream target signalingpathways.

international journal of molecular medicine

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