Apurinic/apyrimidinic endonuclease 1 (APE1) prevents alopecia by promoting regeneration of hair follicles

Abstract

Hair follicle (HF) regeneration, which relies on the self-renewal and differentiation capacity of bulge cells, involves multiple molecular mechanisms. In this study, we found that Apurinic/apyrimidinic endonuclease 1 (APE1) acts as a positive regulator of spontaneous and depilation-induced HF regeneration. Loss of APE1 leads to hair thinning and delayed HF transition from telogen to anagen. As shown in our systematic conditional Apex1 knockout (Apex1^flox/floxCre-ER⁺) mouse model, Apex1^−/− mice gradually lost hair coat over time and eventually became hairless after 10 months. Histological analyses revealed that Apex1 knockout caused the retarded growth of HF and the reduction of hair density, as a result of repressed proliferation of bulge cells by downregulating the β-catenin pathway. Moreover, APE1 is indispensable in the depilation-induced HF regeneration, and its deficiency contributes to the depletion of bulge cells, which in turn causes failure of hair growth. These findings highlight the indispensable role of APE1 for HF activation, maintenance, and growth.