Heparan Sulfate Regulates Hair Follicle and Sebaceous Gland Morphogenesis and Homeostasis

The study investigated the role of Heparan sulfate (HS) in hair follicle (HF) morphogenesis, cycling, and sebaceous gland function using an inducible tetratransgenic mouse model that lacked the enzyme exostosin glycosyltransferase 1 (Ext1) in keratin 14-positive cells from postnatal day 21 (P21). The results showed that mice with the Ext1 deletion (EXT1^StEpiΔ/StEpiΔ) maintained their hair follicles in the growth phase (anagen) and experienced accelerated hair regrowth after waxing, suggesting that HS is involved in the transition to the regression phase (catagen). Additionally, the absence of HS in mature skin led to the spontaneous formation of new hair follicles and increased Sonic Hedgehog expression, which is similar to the process during embryogenesis, indicating that HS normally prevents new HF formation in mature skin. The study also found that HS deficiency caused morphogenesis and hyperplasia of sebaceous and sweat glands, resulting in increased sebum production. These findings demonstrate that HS is crucial for regulating hair follicle development, hair growth cycles, and sebaceous gland homeostasis.