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Published on: March 24, 2017
Fibroblast growth factor 21 improves lipopolysaccharide-induced pulmonary microvascular endothelial cell dysfunction
Xuemei Zhou1, Xinhua Wang2, Lidong Lu1
1Department of Pediatrics, Affiliated Hospital of Jiangnan University, Wuxi 214122, Jiangsu, China.
Insights
Fibroblast growth factor 21 (FGF21) protects lung cells from injury by reducing inflammation and apoptosis. This protective effect is mediated by sirtuin 1 (SIRT1) and its influence on NF-κB signaling pathways.
Area of Science:
- Cell Biology
- Molecular Biology
- Immunology
Background:
- Pneumonia is a leading cause of childhood mortality, often resulting from acute lung injury.
- Fibroblast growth factor 21 (FGF21) is a key regulator of energy homeostasis.
- Understanding FGF21's role in lung injury is crucial for developing new treatments.
Purpose of the Study:
- To investigate the protective effects of FGF21 against lipopolysaccharide (LPS)-induced injury in human pulmonary microvascular endothelial cells (HPMECs).
- To elucidate the underlying molecular mechanisms, focusing on the SIRT1 and NF-κB pathways.
Main Methods:
- Western blotting to analyze protein expression (SIRT1, NF-κB p65, Ac-NF-κB p65, apoptosis, tight junction, adhesion molecules).
- Cell viability (CCK-8) and apoptosis (TUNEL) assays.
- Measurement of lactate dehydrogenase and inflammatory factors.
- RT-qPCR for adhesion molecule mRNA expression.
- Inhibition of SIRT1 using EX527.
Main Results:
- LPS treatment decreased SIRT1 and increased NF-κB p65 and Ac-NF-κB p65 expression in HPMECs.
- Recombinant FGF21 (rFGF21) reversed these changes, improving cell viability and reducing apoptosis, inflammation, permeability, and adhesion molecule release.
- SIRT1 inhibition by EX527 counteracted the protective effects of rFGF21.
Conclusions:
- FGF21 ameliorates LPS-induced HPMEC injury and inflammation.
- The mechanism involves SIRT1-mediated deacetylation of NF-κB.
- FGF21 represents a potential therapeutic agent for pneumonia-related lung injury.
Abstract:
Pneumonia is a common infectious disease of the respiratory system in children. It often leads to death in children by causing acute lung injury. Fibroblast growth factor 21 (FGF21) is a peptide hormone that plays an important role in the regulation of energy homeostasis. This study aimed to investigate the role of FGF21 in alleviating the lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cell (HPMEC) injury, as well as the underlying mechanism. The expression of sirtuin 1 (SIRT1), NF-κB p65, Ac-NF-κB p65, apoptosis-related proteins, tight junction proteins and adhesion molecules in HPMECs were analyzed by Western blotting. The viability and apoptosis of HPMECs were detected by CCK-8 and TUNEL assays. Lactate dehydrogenase level and levels of inflammatory factors were respectively determined by assay kits. The mRNA expression of adhesion molecules in HPMECs was analyzed by RT-qPCR. As a result, SIRT1 expression was decreased and the expression of NF-κB p65 and Ac-NF-κB p65 were increased in LPS-induced HPMECs, which were reversed by recombinant FGF21 (rFGF21). rFGF21 increased the viability and inhibited the apoptosis, inflammatory response, permeability, and release of cell adhesion molecules of LPS-induced HPMECs. In addition, EX527 as SIRT1 inhibitor could reverse the effect of rFGF21 on LPS-induced HPMECs. In conclusion, FGF21 improved LPS-induced HPMEC dysfunction and inflammatory response through SIRT1-mediated NF-κB deacetylation.
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