Autophagy induction regulates aquaporin 3-mediated skin fibroblast ageing

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.

Automated summary

Short-term UVA exposure induces autophagy and upregulates AQP3, while long-term UVA exposure inhibits autophagy, AQP3, and triggers senescence. AQP3 controls skin fibroblast photoageing by regulating autophagy, making it a potential target for future interventions against skin ageing.