水通道蛋白3在皮肤光老化中的机制研究

水通道蛋白3（AQP3）是一种水-甘油通道蛋白。AQP3-/-小鼠出现皮肤干燥、皱缩等衰老表现，但其在细胞衰老中的作用机制鲜有报道。我们的预实验发现，低能量UVA辐射人皮肤成纤维细胞（NHSFs）不足以引起细胞衰老，却能促进自噬和AQP3的表达；而高剂量UVA能诱导细胞衰老，并抑制自噬和AQP3的表达；AQP3沉默后，细胞自噬水平降低，出现衰老表型。我们推测：AQP3可能通过调控自噬在NHSFs光老化过程中起重要作用。本研究中，我们将先调节AQP3表达量，了解其在NHSFs光老化过程中的作用；再利用RNAi等方法探讨自噬在上述过程中的作用；然后从氧化应激、蛋白-蛋白相互作用等角度全面阐述AQP3通过调控自噬影响NHSFs光老化的机制；最后在AQP3敲除小鼠及过表达小鼠体内验证上述机制。最终明确AQP3在NHSFs光老化过程中的作用及机制，为探索皮肤衰老研究领域及治疗方法提供理论依据。

Aquaporin 3 (AQP3) is one of the liquid-glycerol channel proteins. AOP3-/- mice have a dry and shrinking skin. However, there are rarely research reports on its mechanism of cell senescence. Low dose of UVA radiation can promote autophagy and AQP3 expression although it can not induce cellular senescence in normal human skin fibroblasts (NHSFs). On the contrary, high dose of UVA radiation may inhibit autophagy and AQP3 expression and induce cell senescence meanwhile. AQP3 silencing can induce senescence with decreased autophagy in NHSFs. We infer that AQP3 may play an important part in photoaging of NHSFs by regulating autophagy. In the present study, we will clarify the roles of AQP3 in NHSFs photoaging by regulating expression of AQP3. And how autophagy takes part in the mechanism of process stated above will be investigated through RNAi and some other methods. Furthermore, mechanism of how AQP3 effects on NHSFs photoaging through regulating autophagy will be elaborated thoroughly in the aspects of oxidative stress, protein-protein interaction and some other angles. Finally, the mechanism will be verified in AQP3 knockout mice and AQP3 over expression mice in vivo. Our study aims to explore the roles and mechanism of AQP3 on NHSFs photoaging and provide theoretical foundation for the research field and therapeutic field of skin aging.