Hypoxia inducible factor-1a promotes trichogenic gene expression in human dermal papilla cells

Abstract Dermal papilla cells (DPCs) play critical roles in hair follicle development, but the underlying mechanisms that contribute to hair regeneration have yet to be elucidated. In this study, we demonstrated that hypoxia-inducible factor-1a (HIF-1a) is suppressed in scalp tissues of androgenetic alopecia patients and potentially associated with hair follicle development. In DPCs, knockdown of HIF-1a was found to attenuate trichogenic gene expression levels. Under an in vivo mimicked environment in a three-dimensional spheroid culture, HIF-1a-suppressed DPCs downregulated the expression of hair induction-related genes. Finally, treatment with a HIF-1a activator resulted in the elevated expression of trichogenic genes in DPCs. This study highlights the importance of dermal HIF-1a expression in regulating trichogenic genes and provides a promising therapeutic target and a fundamental tissue engineering approach for hair loss treatment.