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Different Biological Pathways Between Good and Poor Inhaled Corticosteroid Responses in Asthma

Gene regulatory networks address how transcription factors (TFs) and their regulatory roles in gene expression determine the responsiveness to anti-asthma therapy. The purpose of this study was to assess gene regulatory networks of adult patients with asthma who showed good or poor lung function imp...

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Autores principales: Kim, Byung-Keun, Lee, Hyun-Seung, Lee, Suh-Young, Park, Heung-Woo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012484/
https://www.ncbi.nlm.nih.gov/pubmed/33816533
http://dx.doi.org/10.3389/fmed.2021.652824
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author Kim, Byung-Keun
Lee, Hyun-Seung
Lee, Suh-Young
Park, Heung-Woo
author_facet Kim, Byung-Keun
Lee, Hyun-Seung
Lee, Suh-Young
Park, Heung-Woo
author_sort Kim, Byung-Keun
collection PubMed
description Gene regulatory networks address how transcription factors (TFs) and their regulatory roles in gene expression determine the responsiveness to anti-asthma therapy. The purpose of this study was to assess gene regulatory networks of adult patients with asthma who showed good or poor lung function improvements in response to inhaled corticosteroids (ICSs). A total of 47 patients with asthma were recruited and classified as good responders (GRs) and poor responders (PRs) based on their responses to ICSs. Genome-wide gene expression was measured using peripheral blood mononuclear cells obtained in a stable state. We used Passing Attributes between Networks for Data Assimilations to construct the gene regulatory networks associated with GRs and PRs to ICSs. We identified the top-10 TFs that showed large differences in high-confidence edges between the GR and PR aggregate networks. These top-10 TFs and their differentially-connected genes in the PR and GR aggregate networks were significantly enriched in distinct biological pathways, such as TGF-β signaling, cell cycle, and IL-4 and IL-13 signaling pathways. We identified multiple TFs and related biological pathways influencing ICS responses in asthma. Our results provide potential targets to overcome insensitivity to corticosteroids in patients with asthma.
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spelling pubmed-80124842021-04-02 Different Biological Pathways Between Good and Poor Inhaled Corticosteroid Responses in Asthma Kim, Byung-Keun Lee, Hyun-Seung Lee, Suh-Young Park, Heung-Woo Front Med (Lausanne) Medicine Gene regulatory networks address how transcription factors (TFs) and their regulatory roles in gene expression determine the responsiveness to anti-asthma therapy. The purpose of this study was to assess gene regulatory networks of adult patients with asthma who showed good or poor lung function improvements in response to inhaled corticosteroids (ICSs). A total of 47 patients with asthma were recruited and classified as good responders (GRs) and poor responders (PRs) based on their responses to ICSs. Genome-wide gene expression was measured using peripheral blood mononuclear cells obtained in a stable state. We used Passing Attributes between Networks for Data Assimilations to construct the gene regulatory networks associated with GRs and PRs to ICSs. We identified the top-10 TFs that showed large differences in high-confidence edges between the GR and PR aggregate networks. These top-10 TFs and their differentially-connected genes in the PR and GR aggregate networks were significantly enriched in distinct biological pathways, such as TGF-β signaling, cell cycle, and IL-4 and IL-13 signaling pathways. We identified multiple TFs and related biological pathways influencing ICS responses in asthma. Our results provide potential targets to overcome insensitivity to corticosteroids in patients with asthma. Frontiers Media S.A. 2021-03-18 /pmc/articles/PMC8012484/ /pubmed/33816533 http://dx.doi.org/10.3389/fmed.2021.652824 Text en Copyright © 2021 Kim, Lee, Lee and Park. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Kim, Byung-Keun
Lee, Hyun-Seung
Lee, Suh-Young
Park, Heung-Woo
Different Biological Pathways Between Good and Poor Inhaled Corticosteroid Responses in Asthma
title Different Biological Pathways Between Good and Poor Inhaled Corticosteroid Responses in Asthma
title_full Different Biological Pathways Between Good and Poor Inhaled Corticosteroid Responses in Asthma
title_fullStr Different Biological Pathways Between Good and Poor Inhaled Corticosteroid Responses in Asthma
title_full_unstemmed Different Biological Pathways Between Good and Poor Inhaled Corticosteroid Responses in Asthma
title_short Different Biological Pathways Between Good and Poor Inhaled Corticosteroid Responses in Asthma
title_sort different biological pathways between good and poor inhaled corticosteroid responses in asthma
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012484/
https://www.ncbi.nlm.nih.gov/pubmed/33816533
http://dx.doi.org/10.3389/fmed.2021.652824
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