Increased expression of dedicator-cytokinesis-10, caspase-2 and Synaptotagmin-like 2 is associated with clinical disease activity in multiple sclerosis
| Autor: | Ricardo Palacios, Ion Agirrezabal, Pablo Villoslada, Sara Llufriu, Antonio Martínez, Albert Saiz, Jorge Sepulcre, Beatriz Moreno, Xavier Montalban, Alice Abernathy, Manuel Comabella, David Arteta |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Neurology Immunology Caspase 2 03 medical and health sciences 0302 clinical medicine Dock10 medicine Immunology and Allergy Prospective cohort study Transcription factor Gene biology business.industry Multiple sclerosis medicine.disease 030104 developmental biology biology.protein Cancer research Biomarker (medicine) Neurology (clinical) business 030217 neurology & neurosurgery |
| Zdroj: | Multiple Sclerosis and Demyelinating Disorders. 1 |
| ISSN: | 2056-6115 |
| DOI: | 10.1186/s40893-016-0009-8 |
| Popis: | We aim to identify differentially expressed genes (DEGs) and its pathways associated with clinical activity of relapsing–remitting Multiple Sclerosis (RRMS). We screened DEG in blood samples from patients with clinically stable or active RRMS (≥2 relapses or increase in ≥1 point in the EDSS (due to relapses) in 2 years follow-up), and healthy controls using DNA arrays. The DEGs identified were validated by RT-PCR in a prospective cohort of MS patients. We used Gene Ontology (GO) analysis for identifying the associated pathways and Jaspar database for identifying the associated transcriptions factors. We identified 45 DEG between the three groups (stable RRMS, active RRMS and control), being 14 of them significantly different between stable and active RRMS. We validated 14 out of the 45 DEG in the second cohort, eight out of the 14 being differentially expressed between active and stable patients (ARHGEF7, CASP2, DOCK10, DSP, ITPR1, KLDHC5, RBBP4, SYTL2). We found an overrepresentation of several pathways associated with lymphocyte activation. The analysis of regulatory networks identified the gene triplet of Dedicator of Cytokinesis-10 (DOCK10) – Caspase-2 (CASP2) - Synaptotagmin-like 2 (SYTL2) as being co-regulated by common transcription factors, pointing to lymphocyte activation pathways associated with disease activity. We describe the triplet DOCK10 - CASP2 - SYTL2 as associated with the clinical activity of RRMS that suggest the role of lymphocyte activation, type 1 interferon and MAPkinase pathways in driving the presence of new relapses and disability accumulation. |
| Databáze: | OpenAIRE |
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