Suppressed expression of T-box transcription factors is involved in senescence in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major global health problem. The etiology of COPD has been associated with apoptosis, oxidative stress, and inflammation. However, understanding of the molecular interactions that modulate COPD pathogenesis remains only partly resolved. We conducted...

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Autores principales:	George K Acquaah-Mensah, Deepti Malhotra, Madhulika Vulimiri, Jason E McDermott, Shyam Biswal
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6a72b1be3de14160b7cd6d7c391cdbd2
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spelling	oai:doaj.org-article:6a72b1be3de14160b7cd6d7c391cdbd22021-11-18T05:51:09ZSuppressed expression of T-box transcription factors is involved in senescence in chronic obstructive pulmonary disease.1553-734X1553-735810.1371/journal.pcbi.1002597https://doaj.org/article/6a72b1be3de14160b7cd6d7c391cdbd22012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22829758/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Chronic obstructive pulmonary disease (COPD) is a major global health problem. The etiology of COPD has been associated with apoptosis, oxidative stress, and inflammation. However, understanding of the molecular interactions that modulate COPD pathogenesis remains only partly resolved. We conducted an exploratory study on COPD etiology to identify the key molecular participants. We used information-theoretic algorithms including Context Likelihood of Relatedness (CLR), Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNE), and Inferelator. We captured direct functional associations among genes, given a compendium of gene expression profiles of human lung epithelial cells. A set of genes differentially expressed in COPD, as reported in a previous study were superposed with the resulting transcriptional regulatory networks. After factoring in the properties of the networks, an established COPD susceptibility locus and domain-domain interactions involving protein products of genes in the generated networks, several molecular candidates were predicted to be involved in the etiology of COPD. These include COL4A3, CFLAR, GULP1, PDCD1, CASP10, PAX3, BOK, HSPD1, PITX2, and PML. Furthermore, T-box (TBX) genes and cyclin-dependent kinase inhibitor 2A (CDKN2A), which are in a direct transcriptional regulatory relationship, emerged as preeminent participants in the etiology of COPD by means of senescence. Contrary to observations in neoplasms, our study reveals that the expression of genes and proteins in the lung samples from patients with COPD indicate an increased tendency towards cellular senescence. The expression of the anti-senescence mediators TBX transcription factors, chromatin modifiers histone deacetylases, and sirtuins was suppressed; while the expression of TBX-regulated cellular senescence markers such as CDKN2A, CDKN1A, and CAV1 was elevated in the peripheral lung tissue samples from patients with COPD. The critical balance between senescence and anti-senescence factors is disrupted towards senescence in COPD lungs.George K Acquaah-MensahDeepti MalhotraMadhulika VulimiriJason E McDermottShyam BiswalPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 7, p e1002597 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 George K Acquaah-Mensah Deepti Malhotra Madhulika Vulimiri Jason E McDermott Shyam Biswal Suppressed expression of T-box transcription factors is involved in senescence in chronic obstructive pulmonary disease.
description	Chronic obstructive pulmonary disease (COPD) is a major global health problem. The etiology of COPD has been associated with apoptosis, oxidative stress, and inflammation. However, understanding of the molecular interactions that modulate COPD pathogenesis remains only partly resolved. We conducted an exploratory study on COPD etiology to identify the key molecular participants. We used information-theoretic algorithms including Context Likelihood of Relatedness (CLR), Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNE), and Inferelator. We captured direct functional associations among genes, given a compendium of gene expression profiles of human lung epithelial cells. A set of genes differentially expressed in COPD, as reported in a previous study were superposed with the resulting transcriptional regulatory networks. After factoring in the properties of the networks, an established COPD susceptibility locus and domain-domain interactions involving protein products of genes in the generated networks, several molecular candidates were predicted to be involved in the etiology of COPD. These include COL4A3, CFLAR, GULP1, PDCD1, CASP10, PAX3, BOK, HSPD1, PITX2, and PML. Furthermore, T-box (TBX) genes and cyclin-dependent kinase inhibitor 2A (CDKN2A), which are in a direct transcriptional regulatory relationship, emerged as preeminent participants in the etiology of COPD by means of senescence. Contrary to observations in neoplasms, our study reveals that the expression of genes and proteins in the lung samples from patients with COPD indicate an increased tendency towards cellular senescence. The expression of the anti-senescence mediators TBX transcription factors, chromatin modifiers histone deacetylases, and sirtuins was suppressed; while the expression of TBX-regulated cellular senescence markers such as CDKN2A, CDKN1A, and CAV1 was elevated in the peripheral lung tissue samples from patients with COPD. The critical balance between senescence and anti-senescence factors is disrupted towards senescence in COPD lungs.
format	article
author	George K Acquaah-Mensah Deepti Malhotra Madhulika Vulimiri Jason E McDermott Shyam Biswal
author_facet	George K Acquaah-Mensah Deepti Malhotra Madhulika Vulimiri Jason E McDermott Shyam Biswal
author_sort	George K Acquaah-Mensah
title	Suppressed expression of T-box transcription factors is involved in senescence in chronic obstructive pulmonary disease.
title_short	Suppressed expression of T-box transcription factors is involved in senescence in chronic obstructive pulmonary disease.
title_full	Suppressed expression of T-box transcription factors is involved in senescence in chronic obstructive pulmonary disease.
title_fullStr	Suppressed expression of T-box transcription factors is involved in senescence in chronic obstructive pulmonary disease.
title_full_unstemmed	Suppressed expression of T-box transcription factors is involved in senescence in chronic obstructive pulmonary disease.
title_sort	suppressed expression of t-box transcription factors is involved in senescence in chronic obstructive pulmonary disease.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/6a72b1be3de14160b7cd6d7c391cdbd2
work_keys_str_mv	AT georgekacquaahmensah suppressedexpressionoftboxtranscriptionfactorsisinvolvedinsenescenceinchronicobstructivepulmonarydisease AT deeptimalhotra suppressedexpressionoftboxtranscriptionfactorsisinvolvedinsenescenceinchronicobstructivepulmonarydisease AT madhulikavulimiri suppressedexpressionoftboxtranscriptionfactorsisinvolvedinsenescenceinchronicobstructivepulmonarydisease AT jasonemcdermott suppressedexpressionoftboxtranscriptionfactorsisinvolvedinsenescenceinchronicobstructivepulmonarydisease AT shyambiswal suppressedexpressionoftboxtranscriptionfactorsisinvolvedinsenescenceinchronicobstructivepulmonarydisease
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Suppressed expression of T-box transcription factors is involved in senescence in chronic obstructive pulmonary disease.

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