皮肤光老化与日光相关免疫性和炎症性皮肤病密切相关，并可导致皮肤肿瘤，故一直为研究热点。晚期糖基化终末产物（AGEs）堆积是其最重要的病理特征之一。既往认为AGEs极难降解，但国外和我们的研究均发现其可被成纤维细胞内吞，并被溶酶体蛋白酶等降解。我们最近的研究不仅证实Cathepsin D(CatD)是降解光老化皮肤AGEs的关键酶及其在光老化皮肤表达降低，还发现环状RNA circLSMs及其对应的海绵吸附miR-23a和miR-27a与CatD表达及自噬密切相关，但它们是否调控CatD表达及其介导的AGEs降解还不清楚。本研究拟采用双荧光素酶报告基因检测、miRNA poll down、三维细胞培养等方法，阐明circLSMs通过海绵吸附miR-23a和或miR-27a调控CatD表达及干预光老化皮肤AGEs堆积。研究结果不仅揭示光老化皮肤AGEs堆积机制，而且可为光老化防治提供新靶点。

Photoaging has increasingly received high interest of research for its close relationship with immunologic and inflammatory dermatoses, and potential carcinogenicity. The accumulation of advanced glycation end products (AGEs) is one of its most important pathological features. AGEs used to be believed to resist degradation. However, foreign studies and our research have found that AGEs can be internalized by fibroblasts, and degraded by lysosomal proteases and others. Recently, cathepsin D (CatD) has been confirmed to be the key protease to degrade AGEs in our laboratory, but its expression is decreased in photoaged skin. Moreover, we have found that circLSMs (circular RNA) and their sponged miR-27a and miR-23a are closely correlated with CatD expression and autophagy. Nevertheless, whether they regulate CatD expression and CatD-mediated AGEs degradation is not yet clarified. This research will investigate whether circLSMs regulate CatD expression and affect AGEs accumulation in photoaged skin through sponging miR-27a and or miR-23a, with the methods of dual luciferase reporter gene assay, miRNA poll down, three-dimensional cell culture, and so on. The results will not only reveal the pathogenesis of AGEs accumulation in photoaging, but also provide a new target for the prevention and treatment of photoaging.