378 Enhanced AQP3 induced by short-term of UVA irradiation prevents skin photoaging through activating autophagy by interacting with DEDD and Beclin1

Long-term and short-term UV exposure have distinct biological impact to human skin. Long-term/high dose UV irradiation causes cutaneous structure deterioration, photoaging and even skin carcinoma, while short-term/low dose UV exposure results in acute adaptive response including photoprotection, inflammation regulation, etcetera. However, the mechanism underlying is rarely studied. Here we demonstrated that short-term of UVA irradiation induced autophagy and aquaporin 3 (AQP3) upregulation, but not cellular senescence. While long-term UVA irradiation resulted in autophagy inhibition and AQP3 repression as well as senescence/aging induction in vitro and in vivo. AQP3 silencing abolish short-term UVA irradiation induced autophagy and led to cellular senescence. Consistently, overexpression of AQP3 partly rescued long-term UVA induced senescence and autophagy inhibition in vitro. Mechanically, transcription factor JUN binds to AQP3’s promoter (+1055 to +1050 from ATG) to activate its transcription after short-term UVA exposure. Subsequently, AQP3 interacts with DEDD to induce DEDD’s ubiquitination degradation and promote autophagy. At the same time, AQP3 protein also binds with Beclin1 to activate autophagy directly. Finally, we found that the autophagy induced by AQP3 overexpression robustly prevents UVA-induced senescence/aging in vitro and in vivo. Our studies here indicate AQP3 is a potential target for future intervention of skin aging.