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Tuesday, November 26, 2024

Hypoxia inducible factor-1α promotes trichogenic gene expression ... - Nature.com

Last updated Friday, January 27, 2023 06:05 ET , Source: NewsService

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 fully elucidated, particularly in terms of alterations in androgenetic alopecia patients. In this study, we demonstrated that hypoxia-inducible factor-1α (HIF-1α) is suppressed in scalp tissues of androgenetic alopecia patients and potentially associated with hair follicle development. Using RT-qPCR and western blot, we found that mRNA and protein levels of trichogenic genes, LEF1 and versican (VCAN), were attenuated in HIF-1α knockdown DPCs. Under an in vivo mimicked environment in a three-dimensional spheroid culture, HIF-1α-suppressed DPCs downregulated the expression of hair induction-related genes. Finally, treatment with a HIF-1α activator resulted in the elevated expression of trichogenic genes in DPCs. This study highlights the importance of dermal HIF-1α expression in regulating trichogenic genes and provides a promising therapeutic target and a fundamental tissue engineering approach for hair loss treatment.

Introduction

The hair follicle is unique to mammals and undergoes cyclic transformations for its entire lifetime1. The development and growth process of hair follicles is regulated by a distinct population of mesenchymal cells, dermal papilla cells (DPCs), which exist in the proximal end of the hair follicle2...



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