The mechanism of GPR120 gene inhibiting NLRP3 inflammasome activation in protection of septic lung injury
10.3969/j.issn.1672-8467.2025.01.006
- VernacularTitle:GPR120基因通过抑制NLRP3炎症小体激活对脓毒症肺损伤保护作用的机制
- Author:
Kai ZHANG
1
;
Yi-qin HUANG
;
Zi-yan ZHANG
;
Lin MI
;
Na YU
;
Zhi-jun BAO
Author Information
1. 复旦大学附属华东医院全科医疗科 上海 200040
- Publication Type:Journal Article
- Keywords:
sepsis;
lung injury;
GPR120 gene;
TUG891;
NLRP3
- From:
Fudan University Journal of Medical Sciences
2025;52(1):44-54
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of the GPR120 gene in the progression of sepsis,explore the molecular mechanisms through which GPR120 gene regulates NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)inflammasome activation and macrophage polarization.Methods The blood and pleural fluid samples were collected from the sepsis patients and the control group.The expression of inflammatory factors and the associated proteins were detected by flow cytometry and ELISA.C57BL/6 mice and monocyte-macrophage cell line(Raw264.7)were treated with lipopolysaccharide(LPS)to construct the sepsis models.After the intervention of GPR120 agonist TUG891,the expression of GPR120 gene,NLRP3 inflammasome protein and macrophage polarization protein were detected between the control group and the sepsis group.Results The expression of inflammatory factors,such as IL-1β in the serum of septic patients,significantly increased compared with the control(P<0.001).And the expression of inflammasome proteins such as NLRP3,Caspase-1 and IL-1β in the pleural fluid also increased(all P<0.05).In vivo,LPS could induce severe inflammation in lung tissue,the GPR120 gene expression decreased in lung tissue,and inflammatory factors were up-regulated in mouse serum(P<0.01).The inflammasome-associated protein and M1 type polarization of macrophages were enhanced,the TUG891 could reduce the inflammatory response,inhibit the NLRP3 inflammasome activating,and promote the M2 polarization of macrophages(P<0.01).In vitro,LPS could inhibit the intracellular GPR120 expression.The inflammatory factors secreted more in LPS-induced sepsis cells.TUG891 could promote the up-regulation of GPR120 protein and alleviate the secretion of inflammatory factors(P<0.05).Conclusion In sepsis,GPR120 gene activation could inhibit the NLRP3 inflammasome activation,promote macrophage polarization,and reduce the inflammatory damage,thereby delay the rapid progression of sepsis.
