Platelet-activating factor-receptor signaling mediates solar-simulated light-induced extracellular vesicle release in human keratinocytes.

Abstract

Ultraviolet (UV) radiation modulates keratinocyte biology through both cytotoxic and signaling-related mechanisms. However, the differential kinetics of UVA versus UVB in regulating extracellular vesicle (EV) release and the underlying mechanisms remain incompletely understood. In this study, we examined the effects of solar-simulated light (SSL; emitting both UVA and UVB) as well as UVA and UVB alone on human HaCaT keratinocytes, focusing on the role of platelet-activating factor-receptor (PAFR) and signaling in both large and small EV release. SSL and UVB induced dose- and time-dependent reductions in cell viability, whereas UVA caused minimal cytotoxicity at equivalent doses, indicating that the UVB component of SSL mediates cytotoxic responses. SSL significantly stimulated early release of large EVs (microvesicle particles, MVPs) and later release of small EVs (exosomes). Similar EV release effects were observed following UVB exposure, but not after UVA exposure. Pharmacological inhibition of PAFR significantly reduced SSL and UVB-induced release of both MVPs and exosomes. Furthermore, inhibition of acid sphingomyelinase (aSMase) or pretreatment with the antioxidant N-acetylcysteine significantly attenuated SSL/UVB-induced EV release. Collectively, these findings indicate PAFR- and aSMase-mediated signaling as key regulators of SSL-dependent keratinocyte EV release and provide mechanistic insight into how solar radiation influences intercellular communication in keratinocytes.