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Modeling Transcriptional Rewiring in Neutrophils Through the Course of Treated Juvenile Idiopathic Arthritis

Neutrophils in children with the polyarticular form of juvenile idiopathic arthritis (JIA) display abnormal transcriptional patterns linked to fundamental metabolic derangements. In this study, we sought to determine the effects of therapy on mRNA and miRNA expression networks in polyarticular JIA....

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Autores principales: Hu, Zihua, Jiang, Kaiyu, Frank, Mark Barton, Chen, Yanmin, Jarvis, James N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958082/
https://www.ncbi.nlm.nih.gov/pubmed/29773851
http://dx.doi.org/10.1038/s41598-018-26163-4
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author Hu, Zihua
Jiang, Kaiyu
Frank, Mark Barton
Chen, Yanmin
Jarvis, James N.
author_facet Hu, Zihua
Jiang, Kaiyu
Frank, Mark Barton
Chen, Yanmin
Jarvis, James N.
author_sort Hu, Zihua
collection PubMed
description Neutrophils in children with the polyarticular form of juvenile idiopathic arthritis (JIA) display abnormal transcriptional patterns linked to fundamental metabolic derangements. In this study, we sought to determine the effects of therapy on mRNA and miRNA expression networks in polyarticular JIA. Using exon and miRNA microarrays, we studied children with untreated active JIA (ADU, n = 35), children with active disease on therapy with methotrexate ± etanercept (ADT, n = 26), and children with inactive disease also on therapy (ID, n = 14). We compared the results to findings from healthy control children (HC, n = 35). We found substantial re-ordering of mRNA and miRNA expression networks after the initiation of therapy. Each disease state was associated with a distinct transcriptional profile, with the ADT state differing the most from HC, and ID more strongly resembling HC. Changes at the mRNA level were mirrored in changes in miRNA expression patterns. The analysis of the expression dynamics from differentially expressed genes across three disease states indicated that therapeutic response is a complex process. This process does not simply involve genes slowly correcting in a linear fashion over time. Computational modeling of miRNA and transcription factor (TF) co-regulatory networks demonstrated that combinational regulation of miRNA and TF might play an important role in dynamic transcriptome changes.
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spelling pubmed-59580822018-05-21 Modeling Transcriptional Rewiring in Neutrophils Through the Course of Treated Juvenile Idiopathic Arthritis Hu, Zihua Jiang, Kaiyu Frank, Mark Barton Chen, Yanmin Jarvis, James N. Sci Rep Article Neutrophils in children with the polyarticular form of juvenile idiopathic arthritis (JIA) display abnormal transcriptional patterns linked to fundamental metabolic derangements. In this study, we sought to determine the effects of therapy on mRNA and miRNA expression networks in polyarticular JIA. Using exon and miRNA microarrays, we studied children with untreated active JIA (ADU, n = 35), children with active disease on therapy with methotrexate ± etanercept (ADT, n = 26), and children with inactive disease also on therapy (ID, n = 14). We compared the results to findings from healthy control children (HC, n = 35). We found substantial re-ordering of mRNA and miRNA expression networks after the initiation of therapy. Each disease state was associated with a distinct transcriptional profile, with the ADT state differing the most from HC, and ID more strongly resembling HC. Changes at the mRNA level were mirrored in changes in miRNA expression patterns. The analysis of the expression dynamics from differentially expressed genes across three disease states indicated that therapeutic response is a complex process. This process does not simply involve genes slowly correcting in a linear fashion over time. Computational modeling of miRNA and transcription factor (TF) co-regulatory networks demonstrated that combinational regulation of miRNA and TF might play an important role in dynamic transcriptome changes. Nature Publishing Group UK 2018-05-17 /pmc/articles/PMC5958082/ /pubmed/29773851 http://dx.doi.org/10.1038/s41598-018-26163-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hu, Zihua
Jiang, Kaiyu
Frank, Mark Barton
Chen, Yanmin
Jarvis, James N.
Modeling Transcriptional Rewiring in Neutrophils Through the Course of Treated Juvenile Idiopathic Arthritis
title Modeling Transcriptional Rewiring in Neutrophils Through the Course of Treated Juvenile Idiopathic Arthritis
title_full Modeling Transcriptional Rewiring in Neutrophils Through the Course of Treated Juvenile Idiopathic Arthritis
title_fullStr Modeling Transcriptional Rewiring in Neutrophils Through the Course of Treated Juvenile Idiopathic Arthritis
title_full_unstemmed Modeling Transcriptional Rewiring in Neutrophils Through the Course of Treated Juvenile Idiopathic Arthritis
title_short Modeling Transcriptional Rewiring in Neutrophils Through the Course of Treated Juvenile Idiopathic Arthritis
title_sort modeling transcriptional rewiring in neutrophils through the course of treated juvenile idiopathic arthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958082/
https://www.ncbi.nlm.nih.gov/pubmed/29773851
http://dx.doi.org/10.1038/s41598-018-26163-4
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