OPN1SW Modulates UVB-Associated DHCR7 Reduction and Associated 25(OH)D3 and Sterol-Pool Responses in Keratinocytes.

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/cm2, 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.