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DC Field | Value | Language |
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dc.contributor.author | Hooper S.B. | en |
dc.contributor.author | Seow B.K.L. | en |
dc.contributor.author | Ng J. | en |
dc.contributor.author | McDougall A.R.A. | en |
dc.contributor.author | Wallace M.J. | en |
dc.contributor.author | Cole T.J. | en |
dc.contributor.author | Short K.L. | en |
dc.contributor.author | Bird A.D. | en |
dc.date.accessioned | 2021-05-14T09:55:28Z | en |
dc.date.available | 2021-05-14T09:55:28Z | en |
dc.date.copyright | 2020 | en |
dc.date.created | 20200420 | en |
dc.date.issued | 2020-04-20 | en |
dc.identifier.citation | Journal of Molecular Endocrinology. 64 (3) (pp 155-164), 2020. Date of Publication: 2020. | en |
dc.identifier.issn | 0952-5041 | en |
dc.identifier.uri | https://repository.monashhealth.org/monashhealthjspui/handle/1/29364 | en |
dc.description.abstract | Glucocorticoid (GC) signaling via the glucocorticoid receptor (GR) is essential for lung maturation in mammals. Previous studies using global or conditional mouse model knockouts of the GR gene have established that GR-mediated signaling in the interstitial mesenchyme of the fetal lung is critical for normal lung development. Screens for downstream GC-targets in conditional mesenchymal GR deficient mouse lung (GRmesKO) identified Versican (Vcan), an important extracellular matrix component and cell proliferation regulator, as a potential GR-regulated target. We show that, of the five major VCAN isoforms, the VCAN-V1 isoform containing the GAGbeta domain is the predominant VCAN isoform in the fetal mouse lung distal mesenchyme at both E16.5 and E18.5, whereas the GAGalpha-specific VCAN-V2 isoform was only localized to the smooth muscle surrounding proximal airways. Both Vcan-V1 mRNA and protein levels were strongly overexpressed in the GRmesKO lung at E18.5. Finally, we investigated the GC regulation of the ECM protease ADAMTS 12 and showed that Adamts 12 mRNA levels were markedly reduced at E18.5 in GRmesKO fetal mouse lung and were strongly induced by both cortisol and betamethasone in cultures of primary rat fetal lung fibroblasts. ADAMTS12 protein immunoreactivity was also strongly increased in the distal lung at E18.5, after dexamethasone treatment in utero. In summary, glucocorticoid signaling via GR represses GAGbeta domain-containing VCAN isoforms in distal lung mesenchyme in vivo by repressing Vcan gene expression and, in part, by inducing the ECM protease ADAMTS12, thereby contributing to the control of ECM remodelling and lung cell proliferation prior to birth.Copyright © 2020 Society for Endocrinology Published by Bioscientifica Ltd. | en |
dc.language | English | en |
dc.language | en | en |
dc.publisher | BioScientifica Ltd. (Euro House, 22 Apex Court, Woodlands, Bradley Stoke, Bristol BS32 4JT, United Kingdom) | en |
dc.relation.ispartof | Journal of Molecular Endocrinology | en |
dc.subject.mesh | immunohistochemistry | - |
dc.subject.mesh | immunoreactivity | - |
dc.subject.mesh | in vivo study | - |
dc.subject.mesh | lung development | - |
dc.subject.mesh | fetus lung maturation | - |
dc.subject.mesh | mRNA expression level | - |
dc.subject.mesh | protein domain | - |
dc.subject.mesh | protein expression level | - |
dc.subject.mesh | protein localization | - |
dc.subject.mesh | real time polymerase chain reaction | - |
dc.subject.mesh | lung fibroblast | - |
dc.subject.mesh | gene expression | - |
dc.subject.mesh | cell proliferation | - |
dc.subject.mesh | extracellular matrix | - |
dc.subject.mesh | fetus | - |
dc.subject.mesh | fetus lung | - |
dc.subject.mesh | signal transduction | - |
dc.subject.mesh | ADAMTS protein | - |
dc.subject.mesh | betamethasone | - |
dc.subject.mesh | dexamethasone | - |
dc.subject.mesh | Gag protein | - |
dc.subject.mesh | glucocorticoid | - |
dc.subject.mesh | glucocorticoid receptor | - |
dc.subject.mesh | hydrocortisone | - |
dc.subject.mesh | isoprotein | - |
dc.subject.mesh | versican | - |
dc.subject.mesh | ADAMTS12 protein | - |
dc.subject.mesh | versican v1 | - |
dc.subject.mesh | versican v2 | - |
dc.title | Glucocorticoid signalling drives reduced versican levels in the fetal mouse lung. | en |
dc.type | Article | en |
dc.identifier.affiliation | Hudson Institute - Centre for Endocrinology and Metabolism | - |
dc.identifier.doi | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1530/JME-19-0235 | - |
dc.publisher.place | United Kingdom | en |
dc.identifier.pubmedid | 31958317 [http://www.ncbi.nlm.nih.gov/pubmed/?term=31958317] | en |
dc.identifier.source | 2004133346 | en |
dc.identifier.institution | (Short, Bird, Seow, Ng, Cole) Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Vicoria, Australia (Bird) Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Monash Medical Centre, Clayton, VIC, Australia (McDougall, Wallace, Hooper) The Richie Centre, Hudson Institute of Medical Research, Monash Medical Centre, Clayton, VIC, Australia | en |
dc.description.address | T.J. Cole, Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Vicoria, Australia. E-mail: tim.cole@monash.edu | en |
dc.description.publicationstatus | Embase | en |
dc.rights.statement | Copyright 2020 Elsevier B.V., All rights reserved. | en |
dc.subect.keywords | glucocorticoid receptors Glucocorticoids Lung development Versican | en |
dc.identifier.authoremail | Cole T.J.; tim.cole@monash.edu | en |
dc.description.grant | Organization: (MU) *Monash University* Organization No: 501100001779 Country: Australia No: 384100 Organization: (NHMRC) *National Health and Medical Research Council* Organization No: 501100000925 Country: Australia | en |
item.fulltext | No Fulltext | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.openairetype | Article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
Appears in Collections: | Articles |
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