Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients
| Autor: | Canan Ulusoy, Hasmet Hanagasi, Elif Sanli, Zerrin Karaaslan, Erdem Tüzün, Ozlem Timirci Kahraman, Cem İsmail Küçükali, Vuslat Yilmaz, Başar Bilgiç, Hayriye Ergen |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Microarray Regulatory T cell Science Neuroimmunology Biology Peripheral blood mononuclear cell T-Lymphocytes Regulatory Article Immunophenotyping Immune system medicine Humans Transcriptomics Gene PI3K/AKT/mTOR pathway Multidisciplinary Parkinson Disease Middle Aged Flow Cytometry Microarray Analysis Molecular biology medicine.anatomical_structure Real-time polymerase chain reaction Gene Ontology Gene chip analysis Leukocytes Mononuclear Medicine Female Protein Binding |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-16 (2021) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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