Abstract
Our aim was to identify the differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMC) of Parkinson’s disease (PD) patients and healthy controls by microarray technology and analysis of related molecular pathways by functional annotation. Thirty PD patients and 30 controls were enrolled. Agilent Human 8X60 K Oligo Microarray was used for gene level expression identification. Gene ontology and pathway enrichment analyses were used for functional annotation of DEGs. Protein–protein interaction analyses were performed with STRING. Expression levels of randomly selected DEGs were quantified by real time quantitative polymerase chain reaction (RT-PCR) for validation. Flow cytometry was done to determine frequency of regulatory T cells (Tregs) in PBMC. A total of 361 DEGs (143 upregulated and 218 downregulated) were identified after GeneSpring analysis. DEGs were involved in 28 biological processes, 12 cellular components and 26 molecular functions. Pathway analyses demonstrated that upregulated genes mainly enriched in p53 (CASP3, TSC2, ATR, MDM4, CCNG1) and PI3K/Akt (IL2RA, IL4R, TSC2, VEGFA, PKN2, PIK3CA, ITGA4, BCL2L11) signaling pathways. TP53 and PIK3CA were identified as most significant hub proteins. Expression profiles obtained by RT-PCR were consistent with microarray findings. PD patients showed increased proportions of CD49d+ Tregs, which correlated with disability scores. Survival pathway genes were upregulated putatively to compensate neuronal degeneration. Bioinformatics analysis showed an association between survival and inflammation genes. Increased CD49d+ Treg ratios might signify the effort of the immune system to suppress ongoing neuroinflammation.
Highlights
Our aim was to identify the differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMC) of Parkinson’s disease (PD) patients and healthy controls by microarray technology and analysis of related molecular pathways by functional annotation
To bring light to possible pathological mechanisms underlying PD and discover biomarkers associated with progression of motor symptoms in PD, we identified differentially expressed genes through microarray and transcriptome studies
Gene ontology analysis (GO) analysis revealed that DEGs were involved in 28 biological processes, 12 cellular components and 26 molecular functions (Table 3)
Summary
Our aim was to identify the differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMC) of Parkinson’s disease (PD) patients and healthy controls by microarray technology and analysis of related molecular pathways by functional annotation. Gene ontology and pathway enrichment analyses were used for functional annotation of DEGs. Protein–protein interaction analyses were performed with STRING. Abbreviations DEGs Differentially expressed genes PD Parkinson’s disease RT-PCR Real time polymerase chain reaction Tregs Regulatory T cells SNpc Substantia nigra pars compacta UPDRS Unified Parkinson disease rating scale H&Y Scale Hoehn and Yahr scale GO Gene ontology KEGG Kyoto Encyclopedia of Genes and Genomes DAVID Database for annotation, visualization and integrated discovery STRING Search tool for the retrieval of interacting genes/proteins ATM Ataxia telangiectasia mutated ATR ATM- and Rad3-related (ATR) MDM2 Murine double minute gene 2 PI3KCA Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha. Evidence of CD4+ T cell infiltration in postmortem studies of PD brain specimens and increased expression of inflammatory cytokines have strengthened the idea that inflammation could be a prominent feature of PD10,11
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