Cholesterol promotes hair growth through activating sympathetic nerves and enhancing the proliferation of hair follicle stem cells.

The regulatory mechanisms by which cholesterol influences hair regeneration remain incompletely understood. This study investigates the effects of cholesterol on hair follicle stem cells (HFSCs) proliferation and hair regeneration, with a focus on the underlying molecular mechanisms. Subcutaneous cholesterol injections in C57BL/6 mice significantly enhanced hair regeneration by promoting HFSCs proliferation. Hematoxylin and eosin (HE) staining revealed a greater number of hair follicles in the anagen phase in the cholesterol-treated group compared to controls. Immunofluorescence (IF) and BrdU labeling further confirmed that cholesterol significantly stimulated HFSCs proliferation. Mechanistically, cholesterol activated the PKA signaling pathway, leading to the phosphorylation of tyrosine hydroxylase (TH) at the serine 40 residue, which subsequently stimulated the sympathetic nervous system (SNS). SNS activation enhanced HFSCs proliferation and increased the proportion of hair follicles in the anagen phase. Furthermore, sympathetic nerve ablation significantly attenuated the hair regeneration-promoting effects of cholesterol, highlighting the critical regulatory role of SNS in this process. These findings provide key insights into the molecular mechanisms by which cholesterol regulates hair regeneration via the PKA-tyrosine hydroxylase-SNS pathway. Moreover, they suggest potential therapeutic applications targeting cholesterol-mediated signaling pathways to promote hair regeneration.