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

作　　者：马明仁 马凌 刘燕[1] 王菲[1] MA Mingren;MA Ling;LIU Yan;WANG Fei(Department of Cardiology,the 940th Hospital of Joint Logistics Support Force of Chinese PLA,Lanzhou 730050,China)

机构地区：[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

出　　处：《西安交通大学学报（医学版）》2024年第5期734-740,共7页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：甘肃省自然科学基金资助项目(No.21JR1RA181,No.GSWSKY2023-47);联勤保障部队第940医院院内项目(No.2021yxky080,No.2021yxky031)。

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。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 

分 类 号：R373[医药卫生—病原生物学]