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

Abstract

Background Acute 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. Methods Recombinant 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. Results The 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. Conclusion These findings indicated a therapeutic role of FGF2 in ALI through ameliorating capillary leakage and inflammation.

An in situ tissue engineering scaffold with growth factors combining angiogenesis and osteoimmunomodulatory functions for advanced periodontal bone regeneration

“…iTE-scaffold abolished the cytokine storms and distinctly stimulated the secretion of pro-healing factors (IL-10 and TGF-β), suggesting a better bone repair potential of the iTE-scaffold. It was reported that bFGF dampened the pro-inflammatory factors production and converted LPS-stimulated inflammatory macrophages polarization into M2 phenotype through AKT/P38/NF-κB pathway [ 16 ]. Furthermore, P-scaffold had no significant effect on reversing LPS-induced M1 macrophages and secretion of inflammatory factors.…”

“…It is an essential growth factor (GF) in wound healing because of its benefits as a powerful inducer of vascularization [ 13 ], proliferation [ 14 ], and migration [ 15 ]. Recently, Pan et al discovered that bFGF could reduce the production of pro-inflammatory factors and promoted lipopolysaccharide (LPS)-stimulated inflammatory macrophages polarization towards anti-inflammatory M2 phenotype through AKT/P38/NF-κB signaling pathways [ 16 ]. Another study reported that bFGF could suppress LPS-mediated inflammatory responses in periodontal ligament stem cells (PDLSCs) ex vivo [ 17 ].…”

Fibroblast growth factor 2 suppresses the expression of C-C motif chemokine 11 through the c-Jun N-terminal kinase pathway in human dental pulp-derived mesenchymal stem cells

“…In particular, FGF2 was found to prevent the neuroinflammation-induced decrease in the phosphorylation of ERK1/2 and alleviated the neuroinflammation-induced impairment in hippocampal neurogenesis (35). In another study, FGF2 improved the survival rate of septic mice by inhibiting the inflammatory response, alleviating lung injury (36). Moreover, FGF2 was reported to stimulate the migration and proliferation of endothelial cells in vivo and to relieve inflammation by inducing the expression of inflammation-related genes, such as proinflammatory cytokines and chemokines in endothelial cells (36)(37)(38).…”

“…In another study, FGF2 improved the survival rate of septic mice by inhibiting the inflammatory response, alleviating lung injury (36). Moreover, FGF2 was reported to stimulate the migration and proliferation of endothelial cells in vivo and to relieve inflammation by inducing the expression of inflammation-related genes, such as proinflammatory cytokines and chemokines in endothelial cells (36)(37)(38). In human DPCs, FGF2 was demonstrated to induce the expression of chemokines, such as IL-6, IL-8, monocyte chemoattractant protein-1α (MIP-1α) and MIP-3α (31).…”

Ultrasound and Microbubbles for Targeted Drug Delivery to the Lung Endothelium in ARDS: Cellular Mechanisms and Therapeutic Opportunities

“…miR-26a-5p, through the reduction in connective tissue growth factor, protected mice with lung injury from lipopolysaccharide (LPS, i.e., endotoxin) by decreasing the severity of inflammation [46]. Finally, fibroblast growth factor 2 and phospholipase D2 have been reported to stabilize VE-cadherin-the former by inhibiting pro-inflammatory pathways, and the latter by preventing VE-cadherin phosphorylation-thereby improving pulmonary endothelial barrier permeability [47,48].…”