Retinoic Acid-Related Orphan Receptor Alpha May Regulate the State of Hair Follicle Stem Cells by Upregulating the Expression of BNIP3.

The hair, an exclusive keratinized dermal appendage in mammals, stands as a quintessential outcome of adaptive evolution, conferring resilience against adverse environmental conditions. The ontogenesis of the coat displays a pronounced rhythmic pattern, with hair follicle stem cells (HFSCs) emerging as pivotal facilitators of hair follicle reconstitution. The retinoic acid-related orphan receptor alpha, a nuclear receptor with extensive involvement in the regulation of cellular physiological states, exerts its functions predominantly through the modulation of downstream target gene transcription. The Bnip3 gene exhibits a robust correlation with cellular apoptosis and autophagy, which are indispensable physiological mechanisms underlying the maintenance of HFSC homeostasis. Consequently, the expression level of Bnip3 may be intimately linked to the status of HFSCs. In this investigative endeavor, we employed rat HFSCs as a model system to validate the regulatory impact of RORA on Bnip3 gene expression. Our findings unequivocally demonstrate that Bnip3 serves as a direct downstream target of RORA. Specifically, RORA binds to the motif within the Bnip3 promoter region, thereby upregulating Bnip3 expression levels. In light of our research findings, we propose that RORA holds potential as a target for modulating the status of HFSCs.