首页|SARS-CoV-2靶向CypA/CD147受体途径诱导心肌细胞凋亡

SARS-CoV-2靶向CypA/CD147受体途径诱导心肌细胞凋亡

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目的 探究SARS-CoV-2靶向亲环素A(CypA)/细胞外金属蛋白酶诱导剂(CD147)受体途径诱导心肌细胞凋亡的可能机制.方法 构建pEncmv-SARS-CoV-2 S-3xflag重组载体质粒转染H9c2细胞,TUNEL实验、流式细胞术和DNA ladder分析细胞凋亡,免疫共沉淀(CoIP)验证CD147与SARS-CoV-2 S蛋白之间相互作用,Western blotting法检测细胞凋亡信号通路相关蛋白表达.结果 与对照组比较,TUNEL实验和流式细胞术结果显示转染组细胞凋亡显著增加(P＜0.05),DNA ladder分析发现DNA降解明显.Western blotting法检测显示Caspase12、DR3表达显著升高(P＜0.001),FAS表达升高(P＜0.01),TRF1、DR4表达降低(P＜0.01).结论 SARS-CoV-2 S蛋白靶向CypA/CD147受体入侵宿主细胞,激活内质网通路(Caspase12)和死亡受体通路(DR3、FAS),以内源性和外源性凋亡途径诱导心肌细胞凋亡.
SARS-CoV-2 induces cardiomyocyte apoptosis by targeting the CypA/CD147 receptor pathway
Objective To explore the possible mechanism of apoptosis induced by SARS-CoV-2 targeting cyclophilin A(CypA)/CD147 receptor pathway.Methods The pEncmv-SARS-CoV-2 S-3xflag recombinant plasmid was constructed and transfected into H9C2 cells.Apoptosis was analyzed by TUNEL assay,flow cytometry and DNA ladder.The interaction between CD147 and SARS-CoV-2 S protein was verified by CoIP.The expressions of apoptosis-related proteins were detected by Western blotting.Results Compared with the control group,TUNEL assay and flow cytometry showed that apoptosis was significantly increased in transfection group(P＜0.05),and DNA ladder analysis showed that DNA degradation was obvious.The expression levels of Caspase12 and DR3 were significantly increased(P＜0.001),the expression level of FAS was slightly increased(P＜0.01),while the expression levels of TRF1 and DR4 were decreased(P＜0.01).Conclusion SARS-CoV-2 S protein targets CypA/CD147 receptor to invade host cells,activate endoplasmic network pathway(Caspase12)and death receptor pathway(DR3,FAS),and induce apoptosis of cardiomyocytes through endogenous and exogenous apoptotic pathways.

severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)coronavirus disease 2019(COVID-19)cyclophilin A(CypA)/CD147cardiomyocytesignaling pathwayapoptosis

马明仁、马凌、刘燕、王菲

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中国人民解放军联勤保障部队第九四○医院心血管内科,甘肃兰州 730050

新型冠状病毒(SARS-CoV-2) 新型冠状病毒肺炎(COVID-19) 亲环素A(CypA)/细胞外金属蛋白酶诱导剂(CD147) 心肌细胞 信号通路 凋亡

甘肃省自然科学基金资助项目甘肃省自然科学基金资助项目联勤保障部队第940医院院内项目联勤保障部队第940医院院内项目

21JR1RA181GSWSKY2023-472021yxky0802021yxky031

2024

10.7652/jdyxb202405006

西安交通大学学报(医学版)
西安交通大学

西安交通大学学报(医学版)

CSTPCD北大核心
影响因子：1.144
ISSN：1671-8259
年,卷(期)：2024.45(5)