Abstract:

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.

Key words:

Dilated cardiomyopathy, CD4+ T cells, miR-155, Endoplasmic reticulum stress

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。

关键词:

扩张型心肌病, CD4+T细胞, miR-155, 内质网应激