Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients

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 co...

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Autores principales:	Zerrin Karaaslan, Özlem Timirci Kahraman, Elif Şanlı, Hayriye Arzu Ergen, Canan Ulusoy, Başar Bilgiç, Vuslat Yılmaz, Erdem Tüzün, Haşmet Ayhan Hanağası, Cem İsmail Küçükali
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c78f37eab31e4824abac58fb8b4fb7f1
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spelling	oai:doaj.org-article:c78f37eab31e4824abac58fb8b4fb7f12021-12-02T10:48:32ZInflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients10.1038/s41598-021-81961-72045-2322https://doaj.org/article/c78f37eab31e4824abac58fb8b4fb7f12021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81961-7https://doaj.org/toc/2045-2322Abstract 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.Zerrin KaraaslanÖzlem Timirci KahramanElif ŞanlıHayriye Arzu ErgenCanan UlusoyBaşar BilgiçVuslat YılmazErdem TüzünHaşmet Ayhan HanağasıCem İsmail KüçükaliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zerrin Karaaslan Özlem Timirci Kahraman Elif Şanlı Hayriye Arzu Ergen Canan Ulusoy Başar Bilgiç Vuslat Yılmaz Erdem Tüzün Haşmet Ayhan Hanağası Cem İsmail Küçükali Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients
description	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.
format	article
author	Zerrin Karaaslan Özlem Timirci Kahraman Elif Şanlı Hayriye Arzu Ergen Canan Ulusoy Başar Bilgiç Vuslat Yılmaz Erdem Tüzün Haşmet Ayhan Hanağası Cem İsmail Küçükali
author_facet	Zerrin Karaaslan Özlem Timirci Kahraman Elif Şanlı Hayriye Arzu Ergen Canan Ulusoy Başar Bilgiç Vuslat Yılmaz Erdem Tüzün Haşmet Ayhan Hanağası Cem İsmail Küçükali
author_sort	Zerrin Karaaslan
title	Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients
title_short	Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients
title_full	Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients
title_fullStr	Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients
title_full_unstemmed	Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients
title_sort	inflammation and regulatory t cell genes are differentially expressed in peripheral blood mononuclear cells of parkinson’s disease patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c78f37eab31e4824abac58fb8b4fb7f1
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Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients

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