m6A识别蛋白HNRNPC通过结合NF-κB上调CD80促肾小管上皮细胞凋亡在脓毒症相关急性肾损伤中的机制研究

脓毒症相关急性肾损伤（S-AKI）是住院和重症患者的常见并发症，死亡率极高，缺乏有效的干预手段。m6A甲基化修饰在AKI中起重要作用，但其在S-AKI发病中的作用尚不明确。我们预实验发现m6A识别蛋白HNRNPC通过“m6A开关”机制可能参与S-AKI进程。.我们利用生信分析、细胞功能验证等方法，建立S-AKI体内外模型进行研究：炎症环境下肾小管上皮细胞CD80表达上调并促细胞凋亡，NF-κB参与CD80转录调控；炎症环境下肾小管上皮细胞m6A修饰水平升高，METTL3介导m6A甲基化修饰；m6A水平依赖性HNRNPC与NF-κB结合，调控下游基因CD80转录促肾小管细胞凋亡。因此我们提出假说：炎症环境下，m6A修饰水平改变，m6A识别蛋白HNRNPC通过结合NF-κB上调CD80，促肾小管上皮细胞凋亡，参与S-AKI的发病机制。.本研究可为干预S-AKI的发病及治疗靶点提供新的分子依据。

Sepsis-related acute kidney injury (S-AKI) is a common complication of hospitalized and critically ill patients, with extremely high mortality and lack of effective interventions. m6A methylation modification plays an important role in AKI, but its role in the pathogenesis of S-AKI is still unclear. Our preliminary experiments found that the m6A recognition protein HNRNPC may participate in the S-AKI process through the "m6A switch" mechanism..We use bio-information analysis and cell function verification to establish S-AKI in vivo and in vitro models for research: renal tubular epithelial cells CD80 expression was up-regulated and promote cell apoptosis in an inflammatory environment, and NF-κB participated in CD80 transcriptional regulation; the m6A modification level of renal tubular epithelial cells was increased under inflammatory conditions, and METTL3 mediated m6A methylation modification; m6A level-dependent HNRNPC binded to NF-κB, and regulated the transcription of downstream gene CD80 to promote renal tubular cell apoptosis. Therefore, we hypothesized that the m6A modification level changes in an inflammatory environment, and the m6A recognition protein HNRNPC up-regulates CD80 by binding to NF-κB, promotes the apoptosis of renal tubular epithelial cells, and participates in the pathogenesis of S-AKI..This study can provide a new molecular basis for intervention in the pathogenesis and therapeutic targets of S-AKI.