非经典分泌因子S100A8/A9的分泌机制研究

许多缺少信号肽的胞质蛋白，可以通过非经典分泌途径被分泌到胞外发挥功能。虽然相关研究比较少，但随着越来越多非经典分泌蛋白的发现，其重要性也越来越凸显。解析蛋白非经典分泌途径和分子机制是目前的研究重点和难点。S100A8/A9是不具有信号肽的分泌蛋白，在胞外发挥多种功能：包括促炎、抗菌、抗氧化和诱导凋亡等。然而，S100A8/A9的分泌机制我们目前很不清楚。新冠病毒感染会导致病人S100A8/A9的表达和分泌上调，且血清中S100A8/A9的水平与病人症状的轻重以及临床结局相关。我们在前期的研究中发现新冠病毒E蛋白的过表达可以促进S100A8/A9的分泌。因此，本项目旨在详细解析S100A8/A9分泌的分子机制以及冠状病毒E蛋白如何调控其分泌。这项研究一方面可以扩展我们对非经典分泌分子机制的认识，另一方面可能为相关疾病的治疗提供理论依据。

Many cytosolic proteins lacking a signal peptide, called leadless proteins, can be secreted to extracellular space to perform their functions by unconventional secretion. Although there are few related researches, the importance of unconventional secretion is becoming more and more prominent with the discovery of more and more unconventional secretory proteins. At present, the focus and difficulty of the research is to resolve the unconventional secretion pathways and molecular mechanisms. S100A8/A9 is a secretory protein without signal peptide, which plays a variety of extracellular functions, including proinflammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. However, the secretory mechanism of S100A8/A9 is poorly understood. SARS-CoV-2 infection leads to upregulation of the expression and secretion of S100A8/A9 in patients, and the level of S100A8/A9 in serum is related to the severity of the patient's symptoms and clinical outcome. In our previously study, we found that overexpression of SARS-CoV-2 Envelope(E) promote the secretion of S100A8/A9. Therefore, this project aims to elucidate the detail molecular mechanism of S100A8/A9 and how the E protein regulates its secretion. The study will expand our understanding of the mechanism of unconventional secretion, and also may provide theoretical basis for the treatment of related diseases.