In vivo effects of dexamethasone on blood gene expression in ataxia telangiectasia View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-01

AUTHORS

Michele Menotta, Sara Biagiotti, Sara Orazi, Luigia Rossi, Luciana Chessa, Vincenzo Leuzzi, Daniela D’Agnano, Alessandro Plebani, Annarosa Soresina, Mauro Magnani

ABSTRACT

Ataxia telangiectasia (AT) is a rare incurable genetic disease caused by biallelic mutations in the Ataxia telangiectasia-mutated gene. Intra-erythrocyte infusion of dexamethasone improves clinical outcomes in AT patients; however, the molecular mechanisms that lead to this improvement remain unknown. Hence, to gain a better understanding of these mechanisms, we assessed the effects of glucocorticoid administration on gene expression in the blood of AT patients. Whole blood was obtained from nine children enrolled in a phase two clinical trial, who were being treated with dexamethasone (AT Dexa), from six untreated AT patients (AT) and from six healthy volunteers (WT). CodeLink Whole Genome Bioarrays were used to assess transcript expression. The reliability of the differentially expressed genes (DEGs) was verified by qRT-PCR analysis. The enriched Gene Ontology (GO) terms and the pathways of the Kyoto Encyclopedia of Genes and Genomes (KEGG) of DEGs obtained by group comparisons were achieved using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Functional network analyses were computed by Reactome FI. The likely involved transcription factors were revealed by iRegulon. Among the identified DEGs influenced by the pathology and restored by dexamethasone, we detected 522 upregulated probes coding for known proteins, while 22 probes were downregulated, as they were in healthy subjects. These results provide useful information and represent a first step towards gaining a better understanding of the underlying mechanisms of the effects of dexamethasone on AT patients. More... »

PAGES

153-166

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11010-017-3122-x

DOI

http://dx.doi.org/10.1007/s11010-017-3122-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1090892512

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28744812


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