Retinoic acid receptor-related orphan receptor ROR? regulates differentiation and survival of keratinocytes during hypoxia.

ABSTRACT: Low O2 pressures present in the microenvironment of epidermis control keratinocyte differentiation and epidermal barrier function through hypoxia inducible factors (HIFs) dependent gene expression. This study focuses on investigating relations of the retinoic acid receptor-related orphan receptor alpha (ROR?) to HIF-1? in keratinocytes under hypoxic conditions. The expression level of ROR? is significantly elevated under hypoxia in both human and murine keratinocytes. Gene silencing of RORA attenuates hypoxia-stimulated expression of genes related to late differentiation and epidermal barrier function, and leads to an enhanced apoptotic response. While the hypoxic induction of ROR? is dependent on HIF-1?, ROR? is in turn critical for nuclear accumulation of HIF-1? and activation of HIF transcriptional activity. These results collectively suggest that ROR? functions as an important mediator of HIF-1? activities in regulating keratinocyte differentiation/survival and epidermal barrier function during the oxygen sensing stage.

SUBMITTER: Li H 

PROVIDER: S-EPMC5610602 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature