BIRC3在TNF-α诱导血管平滑肌细胞表型转化中的作用  

作　　者：郝中伟[1] 刘祖秋 李红敏 胡岩松 罗学胜[1] 

机构地区：[1]中国人民解放军联勤保障部队第九O六医院,315040 [2]中国人民解放军92919部队医院,315000

出　　处：《浙江临床医学》2021年第8期1142-1144,1147,共4页Zhejiang Clinical Medical Journal

基　　金：宁波市医学科技计划项目(2020Y27)。

摘　　要：目的探讨杆状病毒IAP重复序列3(BIRC3)在炎性因子TNF-α诱导血管平滑肌细胞(VSMC)表型转化过程中的作用。方法应用TNF-α处理和正常培养的VSMC转录组测序数据,通过生物信息学分析筛选差异表达基因和相关信号通路。采用qRT-PCR及蛋白免疫印迹验证TNF-α对VSMC中BIRC3表达的影响。TNF-α(10 ng/mL)处理VSMC的同时,采用特异性干扰RNA敲低BIRC3表达,通过qRT-PCR和蛋白免疫印迹法检测α-SMA及MYH11的表达变化,通过平板划线和Transwell实验检测VSMC迁移、侵袭能力。结果差异表达基因在NOD-like信号通路中显著富集(P<0.001,NES=1.64,FDR=0.056),其中BIRC3基因显著上调(logFC=6.3,P<0.01)。TNF-α处理的VSMC中,EIRC3 mRNA和蛋白表达显著上调。干扰敲低EIRC3能够显著抑制TNF-α诱导的α-SMA及MYH11表达下降、VMSC迁移和侵袭。结论TNF-α通过上调BIRC3诱导VSMC表型转化。Objective To investigate the eSect of baculoviral IAP repeat-containing 3(BIRC3)in the phenotypic switching of vascular smooth muscle cell(VSMC)induced by TNF-α.Methods Differentially expressed genes and related pathways were analyzed by bioinfbrmatics using transcriptome sequencing data of normal cultured and TNF-αtreated VSMC.Western blot and qRT-PCR were used to verify the efiect of TNF-α on the expression of BIRC3 in VSMC.Using specific interfering RNA to knock down BIRC3 expression in VSMC treated with TNF-α(10ng/mL).Western blot and qRT-PCR were used to detect the mRNA and protein levels of α-SMA and MYH11.Scratch wound assay was used to detect the migration of VSMC.Transwell assay was used to detect the invasion of VSMC.Results The differentially expressed genes were significantly enriched in the NOD-like signaling pathway(Nominal p-value<0.001,NES=1.64,FDR=0.056),of which BIRC3 is significandy upregulated(logFC=6.3,P<0.01).In VSMC treated with TNF-α,BIRC3 mRNA and protein expression were significantly up-regulated.Interference knockdown of BIRC3 significantly inhibited theα-SMA and MYH11 downregulation,VSMC migration and invasion induced by TNF-α.Conclusion TNF-α induces phenotypic switching of VSMC through upregulating BIRC3 expression.

关 键 词：肿瘤坏死因子α 杆状病毒IAP重复序列3 血管平滑肌细胞 表型转化 

分 类 号：R73[医药卫生—肿瘤]