Abstract

BACKGROUND: Long- and short-term ultraviolet (UV) exposure have distinct biological effects on human fibroblasts. OBJECTIVES: To elucidate the underlying mechanisms of the biological effects of UV exposure on human skin fibroblasts. METHODS: We subjected human skin fibroblast cells with or without aquaporin 3 (AQP3), death effector domain-containing protein (DEDD) or Beclin1 manipulation to UVA treatment and evaluated autophagy and senescence in them. RESULTS: Short-term UVA irradiation induced autophagy and upregulated AQP3 but not senescence, whereas long-term UVA irradiation inhibited autophagy, AQP3 and trigger senescence in vitro and in vivo. Silencing AQP3 abolished short-term UVA irradiation-induced autophagy and led to cellular senescence, whereas AQP3 overexpression partially rescued the senescence and autophagy inhibition induced by long-term UVA exposure in vitro. Mechanistically, the transcription factor Jun was found to bind to the AQP3 promoter to activate its transcription following short-term UVA exposure. Subsequently, AQP3 interacted with DEDD to induce its ubiquitination-mediated degradation and promote autophagy, and bound to Beclin1 to directly activate autophagy. Finally, autophagy induced by AQP3 overexpression robustly prevented UVA-induced senescence in vitro and in vivo. CONCLUSIONS: Our study indicates that AQP3 controls skin fibroblast photoageing by regulating autophagy and represents a potential target for future interventions against skin ageing.