Gene regulation in activated microglia by adenosine A₃ receptor agonists: a transcriptomics study.

IF 3 4区医学 Q2 NEUROSCIENCES Purinergic Signalling Pub Date : 2024-06-01 Epub Date: 2023-01-27 DOI:10.1007/s11302-022-09916-9

Alejandro Lillo, Joan Serrano-Marín, Jaume Lillo, Iu Raïch, Gemma Navarro, Rafael Franco

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Abstract

Most neurodegenerative disorders, including the two most common, Alzheimer's disease (AD) and Parkinson's disease (AD), course with activation of microglia, the resident innate immune cells of the central nervous system. A₃ adenosine receptor (A₃R) agonists have been proposed to be neuroprotective by regulating the phenotype of activated microglia. RNAseq was performed using samples isolated from lipopolysaccharide/interferon-γ activated microglia treated with 2-Cl-IB-MECA, a selective A₃R agonist. The results showed that the number of negatively regulated genes in the presence of 2-Cl-IB-MECA was greater than the number of positively regulated genes. Gene ontology enrichment analysis showed regulation of genes participating in several cell processes, including those involved in immune-related events. Analysis of known and predicted protein-protein interactions showed that Smad3 and Sp1 are transcription factors whose genes are regulated by A₃R activation. Under the conditions of cell activation and agonist treatment regimen, 2-Cl-IB-MECA did not lead to any tendency to favor the expression of genes related to neuroprotective microglia (M2).

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腺苷 A3 受体激动剂对激活的小胶质细胞的基因调控：一项转录组学研究。

大多数神经退行性疾病，包括两种最常见的疾病--阿尔茨海默病（AD）和帕金森病（AD），在发病过程中都会激活中枢神经系统的常驻先天性免疫细胞--小胶质细胞。A3腺苷受体（A3R）激动剂被认为可以通过调节活化的小胶质细胞的表型来保护神经。研究人员用选择性 A3R 激动剂 2-Cl-IB-MECA 处理从脂多糖/干扰素-γ 激活的小胶质细胞中分离的样本进行了 RNAseq 分析。结果显示，2-Cl-IB-MECA 存在时，负调控基因的数量多于正调控基因的数量。基因本体富集分析表明，参与多个细胞过程的基因受到调控，包括参与免疫相关事件的基因。对已知和预测的蛋白质-蛋白质相互作用的分析表明，Smad3 和 Sp1 是转录因子，其基因受 A3R 激活的调控。在细胞激活和激动剂治疗方案的条件下，2-Cl-IB-MECA 不会导致任何有利于神经保护性小胶质细胞（M2）相关基因表达的趋势。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Purinergic Signalling 医学-神经科学

CiteScore

6.60

自引率

17.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Nucleotides and nucleosides are primitive biological molecules that were utilized early in evolution both as intracellular energy sources and as extracellular signalling molecules. ATP was first identified as a neurotransmitter and later as a co-transmitter with all the established neurotransmitters in both peripheral and central nervous systems. Four subtypes of P1 (adenosine) receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of P2Y G protein-coupled receptors have currently been identified. Since P2 receptors were first cloned in the early 1990’s, there is clear evidence for the widespread distribution of both P1 and P2 receptor subtypes in neuronal and non-neuronal cells, including glial, immune, bone, muscle, endothelial, epithelial and endocrine cells.