It is long known that adenosine promotes hair growth. One of the proposed mechanism involves the regulation of hair cycle-associated growth factors production and release by dermal papilla fibroblasts. However, full characterization of the cellular mechanism by which adenosine regulates hair growth cycle, and the distribution of adenosine receptors (ARs) in human hair follicles (HFs), are still poorly understood. Together with scientists of Monasterium Laboratory and our long-term collaborator from the Department of Immunology, Faculty of Medicine at University of Debrecen, Hungary, provide detailed insights on a novel signaling pathway by which adenosine may promote human hair growth in a recent work published in the Journal of Investigative Dermatology (1). Read the full story here.
In this study, scientists employed the highly clinically relevant model, i.e. human microdissected hair follicle ex vivo organ culture, and primary outer root sheath (ORS) keratinocytes in vitro culture.
The first set of experiments revealed that adenosine administration ex vivo significantly stimulated hair shaft elongation and cellular proliferation in the matrix keratinocytes of the hair bulb. In addition, histomorphometric analysis of cultured HFs, showed decreased ratio of HFs in catagen phase and a substantial increase of anagen phase related morphological characteristics, confirming the regulatory effect of adenosine on human hair cycle. Importantly, co-administration of adenosine abolished the inhibitory effect of one of the most potent catagen inducing growth factor, TGF-β2 on hair cycle. Further, by applying molecular techniques and immunofluorescence methods, the results show differential localized expression pattern of ARs (A1, A2A, A2B, A3) in the matrix, ORS, dermal papilla and inner root sheath. Interestingly, isolated keratinocytes from ORS expressed all the four ARs and among them, A2B was the most predominantly expressed.
Lastly, to understand the molecular pathways by which adenosine might regulate human hair growth, the scientists examined gene expression of different positive and negative hair cycle-associated regulators in ORS keratinocytes in vitro. Interestingly, adenosine down-regulated the expression of catagen inducing mediators (TGF-β2 and EGF) and upregulated the expression of stem cell factor and the receptor of the most prominent anagen inducing growth factor, IGF1 in a A2B -dependent manner. Thus, these results reveal that that adenosine regulates hair cycle not only by impacting on dermal papilla fibroblasts but also on outer root sheath keratinocytes in human hair follicles. This certainly highlights the role of intra-follicular adenosine signaling as a potential therapeutic target to treat hair-loss associated diseases and invites additional studies to unravel the complex mechanisms by which adenosine regulates human hair growth.
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References
1. Lisztes E, et al., Adenosine promotes human hair growth and inhibits catagen transition in vitro- role of the outer sheath keratinocytes. J.Invest Dermatol 2019
