Phosphatidylethanolamine promotes macrophage senescence and liver injury by activating endoplasmic reticulum stress
10.3969/j.issn.1674-8115.2025.06.004
- VernacularTitle:磷脂酰乙醇胺引起内质网应激促进巨噬细胞衰老及肝损伤
- Author:
Longchuan HAN
1
;
Yue LI
;
Zhihui ZOU
;
Jing LUO
;
Ruoyi LI
;
Yingting ZHANG
;
Xinxin TANG
;
Lihong TIAN
;
Yuheng LU
;
Ying HUANG
;
Ming HE
;
Yinkun FU
Author Information
1. 上海交通大学基础医学院病理生理学系,细胞分化与凋亡教育部重点实验室,上海市细胞稳态调控与疾病前沿科学研究基地,上海 200025;上海交通大学医学院附属第九人民医院细胞命运与疾病转化医学研究院,上海 200025
- Publication Type:Journal Article
- Keywords:
phosphatidylethanolamine(PE);
macrophage;
senescence-associated secretory phenotype(SASP);
liver injury;
endoplasmic reticulum stress
- From:
Journal of Shanghai Jiaotong University(Medical Science)
2025;45(6):693-704
- CountryChina
- Language:Chinese
-
Abstract:
Objective·To investigate the effects and molecular mechanisms of phosphatidylethanolamine(PE)on macrophage senescence and its senescence-associated secretory phenotype(SASP),as well as its pathophysiological role in liver injury.Methods·A macrophage senescence model was established using doxorubicin(DOX),followed by PE treatment.A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide(LPS)to investigate the effects of PE on liver injury.Senescence markers and SASP factors,including senescence-associated β-galactosidase(SA-β-gal),cell cycle inhibitor p21,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),were evaluated using SA-β-gal staining,quantitative real-time PCR,and Western blotting.RNA sequencing(RNA-seq)was performed,followed by Gene Ontology(GO)cellular component enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis(GSEA),to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence.The expression of endoplasmic reticulum(ER)stress-related proteins,including inositol-requiring enzyme 1 α(IRE1α),spliced X-box binding protein 1(XBP1s),activating transcription factor 6(ATF6),ATF4,and C/EBP homologous protein(CHOP),was analyzed through in vivo and in vitro experiments.Results·PE significantly promoted the expression of senescence markers SA-β-gal,p21,p16 and SASP factors.RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP.Further experiments demonstrated that PE activated the ER stress signaling pathway,promoting macrophage senescence and the expression of SASP factors.In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress.Conclusion·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway,thereby aggravating LPS-induced liver injury.
