西安交通大学学报(医学版)2024,Vol.45Issue(5) :734-740.DOI:10.7652/jdyxb202405006

SARS-CoV-2靶向CypA/CD147受体途径诱导心肌细胞凋亡

SARS-CoV-2 induces cardiomyocyte apoptosis by targeting the CypA/CD147 receptor pathway

马明仁 马凌 刘燕 王菲
西安交通大学学报(医学版)2024,Vol.45Issue(5) :734-740.DOI:10.7652/jdyxb202405006

SARS-CoV-2靶向CypA/CD147受体途径诱导心肌细胞凋亡

SARS-CoV-2 induces cardiomyocyte apoptosis by targeting the CypA/CD147 receptor pathway

马明仁 1马凌 1刘燕 1王菲1
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作者信息

  • 1. 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
  • 折叠

摘要

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.

Abstract

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.

关键词

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

Key words

severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)/coronavirus disease 2019(COVID-19)/cyclophilin A(CypA)/CD147/cardiomyocyte/signaling pathway/apoptosis

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基金项目

甘肃省自然科学基金资助项目(21JR1RA181)

甘肃省自然科学基金资助项目(GSWSKY2023-47)

联勤保障部队第940医院院内项目(2021yxky080)

联勤保障部队第940医院院内项目(2021yxky031)

出版年

2024
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
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