miR-155/Shh/Gli1信号通路在扩张型心肌病CD4+T细胞介导免疫应答中的作用机制  

Mechanism of miR-155/Shh/Gli1 signaling pathway in the immune response mediated by CD4+T cells in dilated cardiomyopathy

作　　者：董福强[1] 滕广帅[2] 霍宁 刘长乐[1] Dong Fuqiang;Teng Guangshuai;Ho Ning;Liu Changle(Department of Cardiology,The Second Hospital of Tianjin Medical University,Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease,Tianjin Institute of Cardiology,Tianjin 300211,China;Department of Hematology,The Second Hospital of Tianjin Medical University,Tianjin 300211,China)

机构地区：[1]天津医科大学第二医院心脏科,天津市心血管病离子与分子机能重点实验室,天津心脏病学研究所,天津300211 [2]天津医科大学第二医院血液科,天津300211

出　　处：《国际医药卫生导报》2025年第3期354-359,共6页International Medicine and Health Guidance News

基　　金：天津市自然科学基金(21JCYBJC01460);天津市教委科研计划(自然科学)(2023KJ028);天津市医学重点学科(专科)建设项目(TJYXZDXK-029A);天津医科大学第二医院重点实验室项目(2019ZDSYS09)。

摘　　要：目的探究CD4+T细胞miR-155/Shh/Gli1信号通路在扩张型心肌病发生发展中的作用机制。方法本研究为临床队列研究。选取2018年1月至2023年12月在天津医科大学第二医院就诊的50例扩张型心肌病患者为DCM组,选取同期同年龄段的50例健康体检人群为健康对照组(HD组)。DCM组男26例,女24例,年龄(49.7±4.9)岁。HD组男25例,女25例,年龄(50.8±4.3)岁。分析CD4+T细胞在扩张型心肌病患者中的表达情况,对不同亚组外周血的CD4+T细胞进行下一代测序(NGS)技术检测,验证信号通路蛋白的表达情况。通过干扰CD4+T细胞中miR-155的表达水平,探究其在扩张型心肌病中的作用机制。统计学方法采用独立样本t检验、Pearson相关性分析。结果DCM组患者的CD4+T细胞水平高于HD组[(45.5±5.9)%比(37.1±6.3)%],差异有统计学意义(t=6.862,P<0.001);miR-155在DCM患者CD4+T细胞中表达高于HD组(P<0.05);miR-155表达升高促进了内质网应激和Hedgehog信号通路中蛋白Shh和Gli1表达升高。使用Shh激动剂处理,可以进一步促进内质网应激反应。结论miR-155/Shh/Gli1信号通路可能参与扩张型心肌病CD4+T细胞异常表达。Objective To explore the mechanism of the miR-155/Shh/Gli1 signaling pathway in CD4+T cells in the pathogenesis and development of dilated cardiomyopathy(DCM).Methods This study was a clinical cohort study.Fifty patients with DCM treated in the Second Hospital of Tianjin Medical University from January 2018 to December 2023 were selected as a DCM group,and 50 healthy subjects of the same age during the same period were selected as a healthy control group(HD group).In the DCM group,there were 26 males and 24 females,aged(49.7±4.9)years.In the HD group,there were 25 males and 25 females,aged(50.8±4.3)years.The expression of CD4+T cells in DCM patients was analyzed,and next generation sequencing(NGS)was performed on CD4+T cells of the peripheral blood from different subgroups to verify the expressions of signaling pathway proteins.The role of miR-155 in DCM was investigated by interfering with its expression level in CD4+T cells.Independent sample t test and Pearson correlation analysis were used for statistical analysis.Results CD4+T cells were actively expressed in DCM patients[(45.5±5.9)%vs.(37.1±6.3)%](t=6.862,P<0.001),and the expression of miR-155 in CD4+T cells was elevated(P<0.05).The increased expression of miR-155 promoted the elevation of endoplasmic reticulum stress(ERS)and the expressions of proteins Shh and Gli1 in the Hedgehog signaling pathway.Treatment with Shhagonists further promoted the ERS response.Conclusion The miR-155/Shh/Gli1 signaling pathway may be involved in the abnormal expression of CD4+T cells in DCM.

关 键 词：扩张型心肌病 CD4+T细胞 MIR-155 内质网应激 

分 类 号：R542.2[医药卫生—心血管疾病]