Fibroblast growth factor-2\xa0alleviates the capillary leakage and inflammation in sepsis

Xiaojun Pan,Fen Wang,Lingjie Mao,Zhen Zhou,Cong Wang,Hao Li,Shunyao Xu,Dequan Li,Jingye Pan,Caixia Wu,Junfeng Wang,Yueyue Huang

doi:10.1186/s10020-020-00221-y

Abstract

BackgroundAcute lung injury (ALI), which is induced by numerous pathogenic factors, especially sepsis, can generate alveolar damage, pulmonary edema and vascular hyper-permeability ultimately leading to severe hypoxemia. Fibroblast growth factor-2 (FGF2) is an important member of the FGF family associated with endothelial cell migration and proliferation, and injury repairment. Here, we conducted this study aiming to evaluate the therapeutic effect of FGF2 in sepsis-induced ALI.MethodsRecombinant FGF2 was abdominally injected into septic mice induced by cecal ligation and puncture (CLP), and then the inflammatory factors of lung tissue, vascular permeability and lung injury-related indicators based on protein levels and gene expression were detected. In vitro, human pulmonary microvascular endothelial cells (HPMEC) and mouse peritoneal macrophages (PMs) were challenged by lipopolysaccharides (LPS) with or without FGF2 administration in different groups, and then changes in inflammation indicators and cell permeability ability were tested.ResultsThe results revealed that FGF2 treatment reduced inflammation response, attenuated pulmonary capillary leakage, alleviated lung injury and improved survival in septic mice. The endothelial injury and macrophages inflammation induced by LPS were inhibited by FGF2 administration via AKT/P38/NF-κB signaling pathways.ConclusionThese findings indicated a therapeutic role of FGF2 in ALI through ameliorating capillary leakage and inflammation.

Highlights

Sepsis, featured by systemic inflammatory response syndrome (SIRS), is caused by infection and can develop into multiple-organ injury, multiple organ failure and shock (Rhodes et al 2017)
Our results showed that Fibroblast growth factor-2 (FGF2) administration reduced the mortality in septic mice (Fig. 1a), which followed by a down-regulation of plasma inflammatory factors (TNF-α and IL-6) expression (Fig. 1b)
The proteome profiler array was conducted to verify that the other elevated cytokines, such as CXCL1, CXCL10, CXCL16, MCP1, MMP8, and IL-10 in the cecal ligation and puncture (CLP) group were decreased by FGF2 treatment (Fig. 1c)

Summary

Introduction

Sepsis, featured by systemic inflammatory response syndrome (SIRS), is caused by infection and can develop into multiple-organ injury, multiple organ failure and shock (Rhodes et al 2017). It is likely that this endothelium disfunction results in a systemic cytokine storm, which causes inflammatory cell infiltration and further promotes inflammation response (Bhattacharya and Matthay 2013). Base on this, treating sepsis by alleviating pulmonary dysfunction is one of the potential therapeutic methods. Therapeutic opinions that can effectively remedy and decrease the mortality of sepsis must be urgently established. Acute lung injury (ALI), which is induced by numerous pathogenic factors, especially sepsis, can generate alveolar damage, pulmonary edema and vascular hyper-permeability leading to severe hypoxemia. We conducted this study aiming to evaluate the therapeutic effect of FGF2 in sepsis-induced ALI

Methods

Results

Discussion

Conclusion