In Toxicology and applied pharmacology ; h5-index 50.0
BACKGROUND : Sepsis is defined as a life-threatening organ dysfunction caused by dysregulation of the host response to infection. There is still a lack of specific treatment for sepsis. Here, we report that Fibroblast growth factor-2 (FGF2) can reduce the mortality of sepsis by ameliorating the coagulation abnormalities.
METHODS : FGF2 was intraperitoneally injected into septic mice induced by lipopolysaccharide (LPS) and then assessed for coagulation response, organ damage and survival. RAW264.7 cells with or without FGF2 pretreating were exposed to LPS, and then changes in coagulation related factors expression and signaling were tested.
RESULTS : The findings showed that intraperitoneal injection of FGF2 inhibited coagulation activity, reduced lung and liver damage, and increased survival in septic mice. In RAW264.7 cells, LPS upregulated the expression of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1); however, pretreatment with FGF2 prevented this upregulation, while FGF2 knockdown exacerbated TF upregulation. Moreover, FGF2 suppressing the AKT/mTOR/S6K1 signaling pathway in septic mice and RAW264.7 cells stimulated by LPS.
CONCLUSIONS : This study revealed a therapeutic role of FGF2 in ameliorating the coagulation abnormalities during sepsis.
Sun Yuanyuan, Ye Fanrong, Li Ding, Yang Hongjing, Xu Tingting, Zhong Xincun, Lu Yilun, Zhou Hongmin, Pan Jingye
2023-Jan-06
Coagulation, DIC, FGF2, PAI-1, Sepsis, TF
