昆明医科大学学报2025，Vol.46Issue(6)：54-63,10.DOI:10.12259/j.issn.2095-610X.S20250607
TP53通过MMP1信号通路促进NIH-3T3焦亡并抑制细胞侵袭及迁移
TP53 Promotes Pyroptosis and Inhibits Cell Invasion and Migration through the MMP1 Signaling Pathway in NIH-3T3 Cells
摘要
Abstract
Objective To explore the molecular mechanism by which TP53 regulating pyroptosis,invasion and migration of embryonic fibroblasts through MMP1/NLRP3 signaling pathway.Methods NIH-3T3 murine embryonic fibroblasts were transfected with lentivirus and grouped as Control,Vector,oeTP53,oeTP53+shNC,and oeTP53+shMMP1.Cell proliferation and viability were assessed via CCK-8 assay,apoptosis by flow cytometry,and migration/invasion through scratch and invasion experiments.Protein interaction between P53 and MMP1 was confirmed by Co-immunoprecipitation.RT-qPCR evaluated mRNA expression of TP53,Collagen Ⅰ,Collagen Ⅲ,and α-SMA,while Western blot analyzed protein levels of these markers and pyroptosis-related proteins.Transmission electron microscopy was employed to examine cellular pyroptotic body modifications.Results Com-pared with Control and Vector groups,the oeTP53 group showed reduced cell proliferation activity(P<0.01),in-creased cell apoptosis rate(P<0.0001),decreased invasion(P<0.0001)and migration capabilities(P<0.0001);reduced Collagen I(P<0.001),Collagen Ⅲ(P<0.01),and α-SMA(P<0.01)protein expressions;increased NLRP3(P<0.05)and cleaved-caspase-1 expressions(P<0.01);and numerous pyroptotic bodies.MMP1 protein levels were found to be elevated in the oeTP53 group(P<0.05),and Co-IP demonstrated an interaction between p53 and MMP1 proteins.Compared with oeTP53 group,the oeTP53+shMMP1 group showed increased cell viability(P<0.001),decreased cell apoptosis rate(P<0.01),and increased cell migration(P<0.01)and invasion capabilities(P<0.01),increased scar formation-related protein expressions of Collagen I(P<0.01),Collagen III(P<0.001),and α-SMA(P<0.05);decreased pyroptosis-related protein expressions of NLRP3(P<0.01)and cleaved-caspase-1(P<0.001);and reduced pyroptotic bodies.Conclusion Overexpression of TP53 can inhibit mouse embryonic fibroblast proliferation,migration,and invasion,reduce scar formation-related protein expressions,and promote cell pyroptosis,with its mechanism potentially related to the MMP1/NLRP3 pathway.关键词
TP53/MMP1/烧伤后瘢痕/瘢痕形成/细胞焦亡Key words
TP53/MMP1/Post-burn scar formation/Scar formation/Pyroptosis分类
医药卫生引用本文复制引用
杨明,吕小星,徐顺利..TP53通过MMP1信号通路促进NIH-3T3焦亡并抑制细胞侵袭及迁移[J].昆明医科大学学报,2025,46(6):54-63,10.基金项目
新乡市科技攻关项目(GG2021047) （GG2021047）
