周围神经损伤再生过程中蛋白质乙酰化修饰的信息解码

本项目对应重点资助研究方向“组织器官再生修复的多维网络信息解码”。由去乙酰化酶和乙酰转移酶调控的蛋白质乙酰化修饰在多种病理生理过程中发挥重要作用，也参与周围神经损伤再生，但其调控机理尚不明了。我们通过抗体富集结合高分辨率质谱，建立了蛋白质乙酰化修饰谱分析方法，并在国际上首次获得坐骨神经蛋白质乙酰化修饰谱。在此基础上，本项目将以神经元轴突再生、施万细胞表型转变及功能变化为切入点，整合基因表达谱、蛋白表达谱、乙酰化修饰谱的系统生物学研究方法，分析周围神经再生过程中蛋白质乙酰化修饰的动态变化，发现关键的乙酰化修饰蛋白及其乙酰化位点，解析其调控网络，探讨有序调节去乙酰化酶及关键蛋白乙酰化修饰对周围神经再生的促进作用。通过研究，将解码周围神经再生过程中蛋白质乙酰化修饰调控的网络信息，阐明其调控机制，为周围神经损伤修复提供新的理论和新的策略。

This project corresponds to the key research direction of "multidimensional network information decoding of tissue and organ regeneration and repair". Protein acetylation, regulated by deacetylase (HDAC/KDAC) and acetyltransferase (HAT/KAT), plays an important role in many pathophysiological processes, as well as in peripheral nerve regeneration. However, the regulatory mechanism is still unclear. In our previous research, we established a mass spectrometry method to analyze the profile of acetylated proteins by antibody enrichment combined with high resolution mass spectrometry. We obtained the acetylome of sciatic nerve. This project will integrate gene expression profile, protein expression profile and acetylation modification profile to analyze the dynamic changes of protein acetylation modifications during peripheral nerve regeneration, find key acetylation modification proteins and their acetylation sites, as well as their regulatory networks. The effect of sequential regulation of HDAC or acetylation of key proteins on the process of peripheral nerve regeneration will also be investigated. This research will decode the network information and regulatory mechanisms of protein acetylation modifications in the process of peripheral nerve regeneration, providing a new theory and a new strategy for the repair of peripheral nerve injury.