Abstract：
Restoring and maintaining the function of endothelial cells is critical for acute respiratory distress syndrome (ARDS). Guanylate binding protein 1(GBP1) is proved to elevated in ARDS patients, but its role and mechanism remains unclear. The objective of this study is to investigate the internal mechanism of GBP1 in lung injury. Our study showed that when the LPS and IFN-γ induced human Pulmonary Microvascular Endothelial Cells (HPMECs) injury model was established, cell viability was significantly reduced, and the levels of GBP1 levels and inflammatory factors were significantly increased. When transfection with si-GBP1, low expression of GBP1 promoted cell proliferation and migration, and decreased the expression of downstream inflammatory factors. Furthermore, the inhibition of GBP1 significantly reduced the occurrence of cell pyroptosis and the expression of NLRP3 and STAT1. Our study indicated that GBP1 alleviates endothelial pyroptosis and inflammation through STAT1 / NLRP3/GSDMD signaling pathway, and GBP1 may be a new target in the treatment of lung injury in the future.
摘要：
恢复和维持内皮细胞的功能对于急性呼吸窘迫综合征（ARDS）至关重要。鸟苷酸结合蛋白1（GBP1）被证明在ARDS患者中升高，但其作用和机制尚不清楚。本研究旨在探讨GBP1在肺损伤中的作用机制。我们的研究表明，当建立LPS和IFN-γ诱导的人肺微血管内皮细胞（HPMECs）损伤模型时，细胞活力显著降低，GBP1水平和炎症因子水平明显升高。si-GBP1转染时,GBP1的低表达促进细胞增殖和迁移,并降低下游炎症因子的表达。此外，GBP1的抑制显著降低了细胞焦亡的发生和NLRP3和STAT1的表达。我们的研究表明，GBP1通过STAT1/NLRP3/GSDMD信号通路减轻内皮细胞的焦化和炎症，GBP1可能是未来肺损伤治疗的新靶点。
