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GSTCD and INTS12 regulation and expression in the human lung

Obeidat, Ma'en ; Miller, Suzanne ; Probert, Kelly ; Billington, Charlotte K ; Henry, Amanda P ; Hodge, Emily ; Nelson, Carl P ; Stewart, Ceri E ; Swan, Caroline ; Wain, Louise V ; Soler Artigas, María ; Melén, Erik ; Ushey, Kevin ; Hao, Ke ; Lamontagne, Maxime ; Bossé, Yohan ; Postma, Dirkje S ; Tobin, Martin D ; Sayers, Ian ; Hall, Ian P Morty, Rory Edward

PloS one, 2013-09, Vol.8 (9), p.e74630 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
GSTCD and INTS12 regulation and expression in the human lung
Autor: Obeidat, Ma'en ; Miller, Suzanne ; Probert, Kelly ; Billington, Charlotte K ; Henry, Amanda P ; Hodge, Emily ; Nelson, Carl P ; Stewart, Ceri E ; Swan, Caroline ; Wain, Louise V ; Soler Artigas, María ; Melén, Erik ; Ushey, Kevin ; Hao, Ke ; Lamontagne, Maxime ; Bossé, Yohan ; Postma, Dirkje S ; Tobin, Martin D ; Sayers, Ian ; Hall, Ian P
Morty, Rory Edward
Assuntos: Airway management ; Alternative splicing ; Analysis ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Chronic obstructive pulmonary disease ; Epidemiology ; Epithelial cells ; Fetuses ; Forced Expiratory Volume - drug effects ; Forced Expiratory Volume - genetics ; Fysiologi ; Gene expression ; Gene Expression Regulation - drug effects ; Gene mapping ; Gene Rearrangement - genetics ; Gene regulation ; Genes ; Genetic Loci - genetics ; Genome, Human - genetics ; Genome-wide association studies ; Genomes ; Genomics ; Glutathione ; Glutathione transferase ; Glutathione Transferase - genetics ; Glutathione Transferase - metabolism ; Health sciences ; Humans ; Intracellular Signaling Peptides and Proteins ; Kinases ; Klinisk medicin ; Lung - cytology ; Lung - embryology ; Lung - metabolism ; Lung - physiology ; Lungmedicin och allergi ; Lungs ; Medicin och hälsovetenskap ; Medicine ; Medicinsk genetik ; Medicinska och farmaceutiska grundvetenskaper ; Muscles ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - metabolism ; Nucleotide Motifs - genetics ; Pneumocytes ; Polymerase Chain Reaction ; Proteins - genetics ; Proteins - metabolism ; Quantitative genetics ; Quantitative trait loci ; Quantitative Trait Loci - genetics ; Respiratory function ; Respiratory tract ; RNA ; RNA polymerase ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Sequence Analysis, DNA ; Single-nucleotide polymorphism ; Smooth muscle ; Studies ; Tissues ; Transcription ; Transcription factors ; Transforming Growth Factor beta1 - pharmacology ; Transforming growth factor-b1 ; Transforming growth factors
É parte de: PloS one, 2013-09, Vol.8 (9), p.e74630
Notas: Competing Interests: The resequencing study performed at the University of Leicester was funded by Pfizer. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
Conceived and designed the experiments: MO SM KP CKB AH EH CPN CES CS LVW MSA EM KU KH ML YB DSP MDT IS IPH. Performed the experiments: MO SM KP CKB AH EH CPN CES CS LVW MSA EM KU KH ML YB DSP MDT IS IPH. Analyzed the data: MO SM KP CKB AH EH CPN CES CS LVW MSA EM KU KH ML YB DSP MDT IS IPH. Contributed reagents/materials/analysis tools: MO SM KP CKB AH EH CPN CES CS LVW EM KU KH ML YB DSP MDT IS IPH. Wrote the manuscript: MO CKB IPH. Approved the final version to be published: MO SM KP CKB AH EH CPN CES CS LVW MSA EM KU KH ML YB DSP MDT IS IPH. Revised the manuscript critically for important intellectual content: MO SM KP CKB AH EH CPN CES CS LVW MSA EM KU KH ML YB DSP MDT IS IPH. Made a substantial contribution to the conception or design of parts of the study: MO SM KP CKB AH EH CPN CES CS LVW MSA EM KU KH ML YB DSP MDT IS IPH. Made a significant contribution in data acquisition or the analysis and interpretation of data: MO SM KP CKB AH EH CPN CES CS LVW MSA EM KU KH ML YB DSP MDT IS IPH.
Descrição: Genome-Wide Association Study (GWAS) meta-analyses have identified a strong association signal for lung function, which maps to a region on 4q24 containing two oppositely transcribed genes: glutathione S-transferase, C-terminal domain containing (GSTCD) and integrator complex subunit 12 (INTS12). Both genes were found to be expressed in a range of human airway cell types. The promoter regions and transcription start sites were determined in mRNA from human lung and a novel splice variant was identified for each gene. We obtained the following evidence for GSTCD and INTS12 co-regulation and expression: (i) correlated mRNA expression was observed both via Q-PCR and in a lung expression quantitative trait loci (eQTL) study, (ii) induction of both GSTCD and INTS12 mRNA expression in human airway smooth muscle cells was seen in response to TGFβ1, (iii) a lung eQTL study revealed that both GSTCD and INTS12 mRNA levels positively correlate with percent predicted FEV1, and (iv) FEV1 GWAS associated SNPs in 4q24 were found to act as an eQTL for INTS12 in a number of tissues. In fixed sections of human lung tissue, GSTCD protein expression was ubiquitous, whereas INTS12 expression was predominantly in epithelial cells and pneumocytes. During human fetal lung development, GSTCD protein expression was observed to be highest at the earlier pseudoglandular stage (10-12 weeks) compared with the later canalicular stage (17-19 weeks), whereas INTS12 expression levels did not alter throughout these stages. Knowledge of the transcriptional and translational regulation and expression of GSTCD and INTS12 provides important insights into the potential role of these genes in determining lung function. Future work is warranted to fully define the functions of INTS12 and GSTCD.
Editor: United States: Public Library of Science
Idioma: Inglês

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GSTCD and INTS12 regulation and expression in the human lung

United States: Public Library of Science

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