老年医学与保健2024，Vol.30Issue(3)：711-720,10.
GPR120基因通过调控NLRP3炎症小体激活保护脓毒症肺损伤的机制研究
The protective mechanism of GPR120 gene against sepsis-induced lung injury by regulating the activation of NLRP3 inflammasome
张凯 1黄一沁 1余纳 2宓林 1张自妍1
作者信息
- 1. 复旦大学附属华东医院全科医疗科,上海 200040
- 2. 复旦大学附属华东医院病理科,上海 200040
- 折叠
摘要
Abstract
Objective To validate the effects of G-protein coupled receptor1 20(GPR120)gene on NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasomes and lung injury by lipopolysaccharide(LPS)-induced sepsis model,and explore its regulatory molecular mechanisms.Methods C57BL/6 mice were used to construct an in vivo sepsis model,and GPR120 gene agonist TUG891 was used to verify the protective effect of GPR120 gene on lung injury in the septic mice.The transcriptome sequencing was performed to screen the differential signaling pathways,and the differential ex-pression of NLRP3 inflammasome and regulatory proteins were verified in the animal models.The Raw264.7 monocyte macro-phage cell line with GPR120 gene over/low-expressed was constructed by lentiviral transfection,and the regulatory effect of GPR120 gene on NLRP3 inflammasome was observed.Results Compared with the sepsis group,the expression of 77 genes including cAMP pathway genes in the lung tissues of mice in the LPS+TUG891 group was significantly up-regulated,and the expression of 37 genes was decreased.The level of GPR120 in the LPS group were significantly lower than that in the normal control group,and the expressions of key proteins CREB and PKA in the cAMP/PKA signaling pathway decreased,and the levels of NLRP3,Caspase-1,IL-1 β and other proteins related to inflammasome activation increased(P＜0.01).After treat-ment with TUG891,the expression of GPR120 in the tissue increased,the cAMP/PKA signaling pathway was reactivated(P＜0.01),and the activation level of NLRP3 inflammasome protein decreased(P＜0.05).In vitro experiments,LPS-induced sepsis caused a decrease in cell proliferation activity,and the expression of GPR120 gene also decreased in septic macrophages(P＜0.001).By intervening the expression of GPR120 gene,it was confirmed that GPR120 gene could negatively regulate the activation levels of NLRP3 inflammasome and cellular inflammatory response(P＜0.01).Conclusion The activation of GPR120 gene can alleviate the inflammatory response and lung injury in sepsis through inhibiting the activation of NLRP3 in-flammasome.关键词
脓毒症/肺损伤/GPR120基因/NOD样受体热蛋白结构域相关蛋白3Key words
sepsis/lung injury/GPR120 gene/NOD-like receptor thermal protein domain associated protein 3(NLRP3)引用本文复制引用
张凯,黄一沁,余纳,宓林,张自妍..GPR120基因通过调控NLRP3炎症小体激活保护脓毒症肺损伤的机制研究[J].老年医学与保健,2024,30(3):711-720,10.
