All-trans-retinoic acid inhibits mink hair follicle growth via inhibiting proliferation and inducing apoptosis of dermal papilla cells through TGF-β2/Smad2/3 pathway

Abstract

Dermal papilla cells (DPCs), an important component of hair follicles, its proliferation and apoptosis directly regulate and maintain the growth of hair follicles. All-trans-retinoic acid (ATRA) plays a critical role in hair growth. In this study, the effects of ATRA on cultured mink hair follicle growth were studied by administration of different concentrations of ATRA for 12 days in vitro. In addition, the proliferation and apoptosis of DPCs were measured after treating with ATRA. The mRNA and protein levels of hair follicle growth associated factor transforming growth factor-β2 (TGF-β2) and the phosphorylation levels of Smad2/3 were determined. Moreover, TGF-β type I and type II receptor inhibitor LY2109761 and specific inhibitor of Smad3 (SIS3) were administered to investigate the underlying molecular mechanism. The results showed that ATRA inhibited hair follicle growth, promoted TGF-β2 expression and activated phosphorylation of Smad2/3. In addition, ATRA inhibited cell proliferation by arresting the cell cycle at G1 phase and induced apoptosis of DPCs by enhancing the ratio of Bax/Bcl-2 and promoted the cleavage of caspase-3. Furthermore, LY2109761 or SIS3 partially reversed the decreased cell viability, increased apoptosis that were induced by ATRA. In conclusion, ATRA could inhibit hair follicle growth via inhibiting proliferation and inducing apoptosis of DPCs partially through the TGF-β2/Smad2/3 pathway.