紫外线（UV）可激活炎性小体引起光损伤，但具体调控机制尚不清楚。项目组前期研究发现：小鼠光损伤皮肤细胞焦亡指标升高；以UVA照射人真皮成纤维细胞（HDF），转录组测序及qRT-PCR发现LNC_003050及STAT6 mRNA上调、相关miRNA下调，生物信息学分析及western blot提示LNC_003050竞争性结合miRNA从而促使STAT6高表达，JASPAR软件预测STAT6可与炎性小体受体启动子结合。据此我们提出假说：UVA通过上调LNC_003050，竞争性结合miRNA，上调STAT6，转录激活炎性小体引起细胞焦亡，导致光损伤。本研究拟以敲除LNC_003050的HDF及小鼠为研究对象，以LNC_003050与STAT6作用关系、STAT6转录激活炎性小体介导细胞焦亡等为研究内容，明确光损伤过程中发挥作用的关键分子，寻找潜在靶标分子，为探索开发新的抗光损伤制剂提供思路

Ultraviolet (UV) may induce skin photodamage by activating inflammasome, but the mechanism remains unclear. Our preliminary data present that certain markers of pyroptosis were overexpressed in photodamaged skin of mice. Transcriptome sequencing analysis and qRT-PCR showed that LNC_003050 and STAT6 mRNA were significantly upregulated and related miRNAs were downregulated in UVA-induced human dermal fibroblasts (HDF). Bioinformatics analysis and western blot suggested that LNC_003050 could competitively bind to miRNA, leading to upregulation of STAT6. The predicted results by the JASPAR software indicated that STAT6 could bind to promoters of inflammasome. Taken together, we hypothesize that UVA may induce skin photodamage through upregulating LNC_003050 which competitively binds to miRNA, promoting STAT6 overexpression, and further activating inflammasome to induce pyroptosis. In this study, we will use LNC_003050-knockout HDF and mice, to identify the relationship between LNC_003050 and STAT6, and to investigate the process of transcriptional activation of STAT6 on inflammasome-mediated pyroptosis. We will try to identify the key molecules involved in UV-induced photodamge, so as to look for potential target molecules to provide preliminary basis for exploring novel anti-photodamage agents.