Anti-Hair Loss Effect of Adenosine Is Exerted by cAMP Mediated Wnt/β-Catenin Pathway Stimulation via Modulation of Gsk3β Activity in Cultured Human Dermal Papilla Cells

In the present study, we investigated the molecular mechanisms of adenosine for its hair growth promoting effect. Adenosine stimulated the Wnt/beta-catenin pathway by modulating the activity of Gsk3 beta in cultured human dermal papilla cells. It also activated adenosine receptor signaling, increasing intracellular cAMP level, and subsequently stimulating the cAMP mediated cellular energy metabolism. The phosphorylation of CREB, mTOR, and GSK3 beta was increased. Furthermore, the expression of beta-catenin target genes such as Axing, Lef1, and growth factors (bFGF, FGF7, IGF-1) was also enhanced. The inhibitor study data conducted in Wnt reporter cells and in cultured human dermal papilla cells demonstrated that adenosine stimulates Wnt/beta-catenin signaling through the activation of the adenosine receptor and Gsk3 beta plays a critical role in transmitting the signals from the adenosine receptor to beta-catenin, possibly via the Gocs/cAMP/PKA/mTOR signaling cascade.