ABSTRACT Ultraviolet B (UVB) irradiation initiates cutaneous vitamin D‐related photochemistry from 7‐dehydrocholesterol (7‐DHC), which is also the immediate precursor of cholesterol via 7‐dehydrocholesterol reductase (DHCR7). Thus, DHCR7 occupies a branch‐point position linking cholesterol biosynthesis and UVB‐associated vitamin D‐related metabolism. How keratinocytes regulate this metabolic relationship under UVB remains unclear. We examined whether OPN1SW is associated with DHCR7 protein abundance, conditioned medium 25‐hydroxyvitamin D3 25(OH)D3 (a vitamin D‐related readout) and sterol‐pool responses in UVB‐exposed keratinocytes. A UVB dose that preserved > 80% cell viability, 10 mJ/cm 2 , increased OPN1SW protein abundance and reduced DHCR7 protein abundance in human epidermal keratinocytes and HaCaT cells. These changes were accompanied by increased conditioned medium 25(OH)D3 and a reduced cellular sterol‐pool readout. OPN1SW overexpression increased DHCR7 protein abundance under basal conditions. Under UVB exposure, OPN1SW overexpression attenuated UVB‐associated DHCR7 reduction, attenuated the UVB‐associated increase in conditioned medium 25(OH)D3 and partially preserved the sterol‐pool readout. Conversely, OPN1SW knockdown exacerbated DHCR7 reduction under UVB and was accompanied by higher conditioned medium 25(OH)D3 and a lower sterol‐pool readout. DHCR7 knockdown produced concordant shifts in these readouts, supporting a contributory role for DHCR7. Together, these findings support the presence of a UVB‐responsive OPN1SW‐DHCR7 module that may contribute to keratinocyte adaptation to UVB exposure.
Yang et al. (Mon,) studied this question.