最新发现：冷休克蛋白Lin28与细胞焦亡密切相关，caspase-8/3介导的焦亡是调控动脉粥样硬化（AS）中内皮炎症的新机制。课题组发现：Lin28在AS的主动脉内皮细胞中高表达且质膜形成焦亡孔道，但是Lin28及其翻译后修饰与细胞焦亡关系和调控机制仍不清楚。因此我们假设：Lin28翻译后修饰调控AS过程中内皮细胞焦亡，其机制依赖caspase-8/3通路。本研究应用单细胞转录组学筛选Lin28调控与焦亡相关的差异基因，结合筛选信息和基因修饰AS模型，明确Lin28对AS过程中内皮细胞焦亡的作用；再研究Lin28通过caspase家族不同亚型调控细胞焦亡，阐明Lin28调控机制是依赖caspase-8/3剪切焦亡执行蛋白GSDMD和GSDME；进一步研究Lin28乙酰化/脂肪酰化修饰和修饰位点对其调控焦亡的影响，揭示Lin28翻译后修饰与细胞焦亡的关系，为AS防治和新药研究提供实验依据。

Recent studies found that the cold shock protein Lin28 regulates endothelial cell pyroptosis, and caspase-8/3-mediated cell pyroptosis is a new mechanism of regulating endothelial cell inflammation in atherosclerosis. We found that Lin28 was overexpressed in aortic endothelium and pyroptosis forms pores in membranes was found in atherosclerosis. However, whether cell pyroptosis is regulated by post-translational modification of Lin28 and related mechanism during atherogenesis remains elusive. Therefore, we hypothesize that post-translational modification of Lin28 regulates endothelial cell pyroptosis in atherosclerosis through caspase-8/3-mediated pathway. In the present study, the single cell transcriptome is first used to screen the differential genes of cell pyroptosis regulated by Lin28. And we determine the effect of Lin28 on endothelial cell pyroptosis during atherogenesis in gene-modified mice and vascular endothelial cells. Then, we investigate Lin28 regulates cell pyroptosis through caspase-8/3-mediated pyroptosis executor GSDMD and GSDME. Further study will be performed to determine the effects of acetylation and fat acylation modifications of Lin28 and related modification sites on cell pyroptosis in AS. The study focuses on the effect of post-translational modification of Lin28 on cell pyroptosis and provides the experimental and theoretical foundation for prevention and treatment of AS and new drug discovery.