WTAP介导的甲基转移酶复合物METTL3-METTL14激活调控脓毒症肺微血管内皮损伤中hnRNP A2/B1 mRNA m6A甲基化修饰

脓毒症肺损伤是ICU患者的重要死因，降低脓毒症肺损伤的死亡率是亟待解决的临床问题，但其相关的病理生理机制尚不明确。肺微血管内皮损伤在脓毒症肺损伤中发挥关键作用，我们前期研究发现：hnRNP A2/B1在脓毒症肺损伤小鼠的肺微血管内皮细胞中发挥保护作用（待发表）。此外，我们还发现，肺微血管内皮细胞中hnRNP A2/B1的表达在脓毒症肺损伤早期显著增高，随后迅速降低，提示hnRNP A2/B1的表达存在负反馈调控机制。我们预实验发现，脓毒症肺损伤后期hnRNP A2/B1表达下调与其mRNA发生m6A甲基化修饰相关，但具体的调控机制目前未知。因此，本研究拟探讨hnRNP A2/B1 mRNA m6A甲基化修饰的可能机制，从而为脓毒症肺损伤的病生理机制研究提供基础，为脓毒症肺损伤的治疗提供新的靶点。

Sepsis-induced lung injury, as the main cause of death in ICU patients, is an important clinical issue to be managed. However, the pathophysiological mechanism of sepsis-induced lung injury remains unclear. Pulmonary microvascular endothelial injury is critical to the pathogenesis of ALI during sepsis. Our previous work found that hnRNP A2/B1 could protect pulmonary microvascular endothelial cells against the impairment from sepsis-induced lung injury in mice (under review). Moreover, we also found that hnRNP A2/B1 expression in pulmonary endothelial cells was significantly induced by sepsis, and then quickly declined, suggesting that negative feedback regulatory loop is important for the regulation of hnRNP A2/B1 expression. Our pilot data showed that down-regulation of hnRNP A2/B1 expression in the late phase of sepsis-induced lung injury was significantly inverse-correlated with m6A modification of its mRNA, but it remains unknown for the regulatory mechanisms. Thus, we intend to investigate the underlying mechanisms responsible for the hnRNP A2/B1 mRNA m6A modification, so as to suggest new mechanisms and therapeutic targets for sepsis-induced lung injury.