دورية أكاديمية
Transcriptome analysis of controlled and therapy-resistant childhood asthma reveals distinct gene expression profiles
| العنوان: | Transcriptome analysis of controlled and therapy-resistant childhood asthma reveals distinct gene expression profiles |
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| المؤلفون: | Persson, Helena, Kwon, Andrew T., Ramilowski, Jordan A., Silberberg, Gilad, Soderhall, Cilla, Orsmark-Pietras, Christina, Nordlund, Bjorn, Konradsen, Jon R., de Hoon, Michiel J. L., Melen, Erik, Hayashizaki, Yoshihide, Hedlin, Gunilla, Kere, Juha, Daub, Carsten O. |
| المساهمون: | Research Programs Unit, Juha Kere / Principal Investigator, Research Programme for Molecular Neurology |
| بيانات النشر: | Mosby Elsevier |
| سنة النشر: | 2017 |
| المجموعة: | Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| مصطلحات موضوعية: | Therapy-resistant asthma, childhood asthma, peripheral blood leukocytes, transcriptome, long noncoding RNA, PROBLEMATIC SEVERE ASTHMA, GENOME-WIDE ASSOCIATION, DIFFERENTIAL EXPRESSION, CHILDREN, EXACERBATIONS, PHENOTYPES, CELLS, LOCI, SETS, Biomedicine |
| الوصف: | Background: Children with problematic severe asthma have poor disease control despite high doses of inhaled corticosteroids and additional therapy, leading to personal suffering, early deterioration of lung function, and significant consumption of health care resources. If no exacerbating factors, such as smoking or allergies, are found after extensive investigation, these children are given a diagnosis of therapy-resistant (or therapy-refractory) asthma (SA). Objective: We sought to deepen our understanding of childhood SA by analyzing gene expression and modeling the underlying regulatory transcription factor networks in peripheral blood leukocytes. Methods: Gene expression was analyzed by using Cap Analysis of Gene Expression in children with SA (n = 13), children with controlled persistent asthma (n = 15), and age-matched healthy control subjects (n = 9). Cap Analysis of Gene Expression sequencing detects the transcription start sites of known and novel mRNAs and noncoding RNAs. Results: Sample groups could be separated by hierarchical clustering on 1305 differentially expressed transcription start sites, including 816 known genes and several novel transcripts. Ten of 13 tested novel transcripts were validated by means of RT-PCR and Sanger sequencing. Expression of RAR-related orphan receptor A (RORA), which has been linked to asthma in genome-wide association studies, was significantly upregulated in patients with SA. Gene network modeling revealed decreased glucocorticoid receptor signaling and increased activity of the mitogen-activated protein kinase and Jun kinase cascades in patients with SA. Conclusion: Circulating leukocytes from children with controlled asthma and those with SA have distinct gene expression profiles, demonstrating the possible development of specific molecular biomarkers and supporting the need for novel therapeutic approaches. ; Peer reviewed |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| ردمك: | 978-84-941178-7-9 84-941178-7-4 |
| العلاقة: | Supported by a research grant for the RIKEN Omics Science Center from MEXT (to Y.H.) and grants from the Swedish Foundation for Strategic Research (RBc08-0027) and the Swedish Research Council (2009-5091; to J.K.). Patient sample collection was supported by grants from the Freemason Child House Foundation in Stockholm, the Konsul Th. C. Bergh's Foundation, the Swedish Asthma and Allergy Association's Research Foundation, the Centre for Allergy Research at Karolinska Institutet, the Swedish Heart-Lung Foundation, Karolinska Institutet, and the Bernard Osher Initiative for Research on Severe Asthma.; Persson , H , Kwon , A T , Ramilowski , J A , Silberberg , G , Soderhall , C , Orsmark-Pietras , C , Nordlund , B , Konradsen , J R , de Hoon , M J L , Melen , E , Hayashizaki , Y , Hedlin , G , Kere , J & Daub , C O 2015 , ' Transcriptome analysis of controlled and therapy-resistant childhood asthma reveals distinct gene expression profiles ' , Journal of Allergy and Clinical Immunology , vol. 136 , no. 3 , pp. 638-648 . https://doi.org/10.1016/j.jaci.2015.02.026Test; http://hdl.handle.net/10138/203739Test; 985b33d0-bf8a-4b92-9fa9-b3d50a905d68; 84941178746; 000360913300014 |
| الإتاحة: | http://hdl.handle.net/10138/203739Test |
| حقوق: | cc_by_nc_nd ; info:eu-repo/semantics/openAccess ; openAccess |
| رقم الانضمام: | edsbas.622B5EAA |
| قاعدة البيانات: | BASE |
| ردمك: | 9788494117879 8494117874 |
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