The Adenosine-Generating Ecto-Enzyme CD73 Regulates Human Hair Growth

    Lucas Moya, Marta Bertolini, Youhei Uchida, K. Figlak, Jérémy Chéret, Herman Waldmann, Ralf Paus
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    TLDR The enzyme CD73 helps control human hair growth and could be targeted to treat hair growth disorders.
    The study investigated the role of the ecto-5'-nucleotidase CD73 in human hair growth, hypothesizing that CD73, which metabolizes AMP to adenosine, might impact hair follicle (HF) growth. CD73 was found to be strongly expressed in the HF mesenchyme and epithelium. Using the CD73-specific antagonist APCP, researchers observed a strong inhibition of hair shaft production and induction of catagen development, with the effective concentration varying between 25µM to 100µM among patients. Additionally, a decrease in adenosine concentration in the medium was associated with reduced hair elongation after APCP treatment, suggesting that the inhibition of elongation might result from reduced adenosine production by CD73. This was further supported by pilot experiments showing that the inhibition could be reversed by treating HFs with APCP in combination with 0.1 μM adenosine. Silencing CD73 in the mesenchyme did not affect hair shaft production or catagen transition, indicating that intrafollicular CD73 activity in the HF epithelium is crucial for hair growth control. The study concludes that CD73 activity is a novel endogenous regulator of human hair growth, potentially by modulating anagen-prolonging adenosine within the HF epithelium, and suggests that CD73 could be a therapeutic target for managing hair growth disorders.
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