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帕金森病肠道 CD4+T 细胞中 miRNA-mRNA 病理调控网络的综合分析。

Comprehensive Analysis of the miRNA-mRNA Pathological Regulatory Network of Intestinal CD4 + T Cells in Parkinson's Disease.

机构信息

Department of Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou , Jiangsu, 221004, China.

Department of Neurology, The Affiliated Huai'an Hospital of Xuzhou Medical Universityand, The Second People's Hospital of Huai'an , Jiangsu, 223022, Huai, China.

出版信息

J Mol Neurosci. 2023 Aug;73(7-8):529-538. doi: 10.1007/s12031-023-02132-z. Epub 2023 Jun 24.

Abstract

Infiltration of CD4 + T cells was found in brain tissue samples from PD patients, suggesting their involvement in developing central nervous system (CNS) disease. The idea of the gut-brain axis further corroborates intestinal T cells' activation as the central immune response initiation. However, the specific factors and molecular pathways regulating intestinal T-cell activation are unclear. We used the GSE156287 and GSE145814 datasets from the GEO database to analyze and obtain the miRNAs, which are aberrantly expressed in intestinal CD4 + T cells in PD patients and predict their regulatory target mRNAs. Further, combined with the GSE174473 dataset of CD4 + T cells sequencing in PD patients, we finally clarified the aberrant genes expressed in CD4 + T cells from the intestine of PD patients and constructed a miRNA-mRNA regulatory network. The highlight of our findings showed pathways, networks, biological functions, and key molecules potentially involved in the miRNA-mediated functional effects in CD4 + T cell from the intestine of PD patients. The hsa-miR-3180-3p mediated CBX8, etc. were determined as most effective in enhancing T cell survival. PEG10, etc. regulated by hsa-miR-20a-3p targets were possibly involved in T cell differentiation. The JPT2 regulated by hsa-miR-1281 were involved in influencing T cell infiltration. The discovery of this interaction between miRNA and mRNA in CD4 + T cell has important implications for understanding the intestinal initial of PD pathological molecular and anti-inflammation of T cell activation.

摘要

在 PD 患者的脑组织样本中发现了 CD4+T 细胞浸润,表明它们参与了中枢神经系统(CNS)疾病的发生。肠道-大脑轴的概念进一步证实了肠道 T 细胞的激活是中枢免疫反应的启动。然而,调节肠道 T 细胞激活的特定因素和分子途径尚不清楚。我们使用 GEO 数据库中的 GSE156287 和 GSE145814 数据集进行分析,获得了 PD 患者肠道 CD4+T 细胞中异常表达的 miRNAs,并预测了其调节的靶 mRNAs。此外,结合 PD 患者肠道 CD4+T 细胞测序的 GSE174473 数据集,我们最终阐明了 PD 患者肠道 CD4+T 细胞中异常表达的基因,并构建了 miRNA-mRNA 调控网络。我们研究的重点是阐明 PD 患者肠道 CD4+T 细胞中可能涉及 miRNA 介导的功能效应的途径、网络、生物学功能和关键分子。hsa-miR-3180-3p 介导的 CBX8 等被确定为增强 T 细胞存活最有效的分子。由 hsa-miR-20a-3p 调控的 PEG10 等可能参与 T 细胞分化的调节。由 hsa-miR-1281 调控的 JPT2 可能参与影响 T 细胞浸润。这项关于 CD4+T 细胞中 miRNA 和 mRNA 之间相互作用的发现,对于理解 PD 发病的肠道初始阶段的病理分子和 T 细胞激活的抗炎作用具有重要意义。

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