Androgens modify Wnt agonists/antagonists expression balance in dermal papilla cells preventing hair follicle stem cell differentiation in androgenetic alopecia

GUSTAVO J. LEIROS; JULIETA M. CERUTI; MARÍA LÍA CASTELLANOS; ANA GABRIELA KUSINSKY; MARÍA EUGENIA BALAÑA

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2017 vol. 439C p. 26 - 34

0303-7207

In androgenetic alopecia, androgens impair dermal papilla-induced hair follicle stem cell (HFSC) differentiationinhibiting Wnt signaling. Wnt agonists/antagonists balance was analyzed after dihydrotestosterone(DHT) stimulation in androgen-sensitive dermal papilla cells (DPC) cultured as spheroidsor monolayer. In both culture conditions, DHT stimulation downregulated Wnt5a and Wnt10b mRNAwhile the Wnt antagonist Dkk-1 was upregulated. Notably, tissue architecture of DPC-spheroids lowersDkk-1 and enhances Wnt agonists´ basal expression; probably contributing to DPC inductivity. The role ofWnt agonists/antagonists as mediators of androgen inhibition of DPC-induced HFSC differentiation wasevaluated. Inductive DPC-conditioned medium supplemented with DKK-1 impaired HFSC differentiationmimicking androgens´ action. This effect was associated with inactivation of Wnt/b-catenin pathway indifferentiating HFSC by both DPC-conditioned media. Moreover, addition of WNT10b to DPC-mediumconditioned with DHT, overcame androgen inhibition of HFSC differentiation. Our results identifyDKK1 and WNT10b as paracrine factors which modulate the HFSC differentiation inhibition involved inandrogen-driven balding.