Intensive Care Unit, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Biochem Biophys Res Commun. 2022 Dec 17;634:152-158. doi: 10.1016/j.bbrc.2022.09.112. Epub 2022 Oct 3.
Acute lung injury (ALI), with high morbidity and mortality, is mainly resulted by infectious or non-infectious inflammatory stimulators, and it will further evolve into acute respiratory distress syndrome if not controlled. Fibroblast growth factors (FGFs) consist of more than 23 kinds of members, which are involved in various pathophysiological processes of body. However, the effect of FGF5, one member of FGFs, is still not certain in lipopolysaccharide (LPS)-induced ALI. In this study, we explored the possible impacts of FGF5 in LPS-induced ALI and primarily focused on endothelial cell, which was one of the most vulnerable cells in septic ALI. In the mouse group of FGF5 overexpression, LPS-induced lung injuries were mitigated, as well as the pyroptosis levels of pulmonary vascular endothelial cells. Additionally, in vitro human umbilical vein endothelial cells (HUVECs), our results showed that the level of cell pyroptosis was ameliorated with FGF5 overexpression, and AKT signal was activated with the overexpression of FGF5, whereas after administration of MK2206, an inhibitor of AKT signal, the protection of FGF5 was inhibited. Therefore, these results suggested that FGF5 exerted protective effects in endothelial cells exposed to LPS, and this protection of FGF5 could be attributed to activated AKT signal.
急性肺损伤（ALI）发病率和死亡率高，主要由感染性或非感染性炎症刺激物引起，如果得不到控制，将进一步发展为急性呼吸窘迫综合征。成纤维细胞生长因子（FGFs）由 23 多种成员组成，参与机体的各种病理生理过程。然而，FGFs 成员之一 FGF5 在脂多糖（LPS）诱导的 ALI 中的作用尚不确定。在本研究中，我们探讨了 FGF5 在 LPS 诱导的 ALI 中的可能作用，主要集中在血管内皮细胞上，它是脓毒症 ALI 中最脆弱的细胞之一。在 FGF5 过表达的小鼠组中，LPS 诱导的肺损伤减轻，肺血管内皮细胞的细胞焦亡水平也降低。此外，在体外人脐静脉内皮细胞（HUVECs）中，我们的结果表明，FGF5 过表达可改善细胞焦亡水平，而过表达 FGF5 可激活 AKT 信号，而给予 AKT 信号抑制剂 MK2206 后，FGF5 的保护作用被抑制。因此，这些结果表明，FGF5 在暴露于 LPS 的内皮细胞中发挥保护作用，FGF5 的这种保护作用可能归因于激活的 AKT 信号。
