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dc.contributor.authorJohnson, ZI
dc.contributor.authorGogate, SS
dc.contributor.authorDay, R
dc.contributor.authorBinch, A
dc.contributor.authorMarkova, DZ
dc.contributor.authorChiverton, N
dc.contributor.authorCole, A
dc.contributor.authorShapiro, IM
dc.contributor.authorLe Maitre, CL
dc.contributor.authorRisbud, MV
dc.contributor.authorConner, Matthew T.
dc.date.accessioned2019-05-13T11:45:25Z
dc.date.available2019-05-13T11:45:25Z
dc.date.issued2015-03-20
dc.identifier.citationJohnson, Z. I., Gogate, S. S., Day, R., Binch, A., Dessislava Z. M., Chiverton, N., Cole, A., Conner, M., Shapiro, I. M., Le Maitre, C. L. and Risbud, M. V. (2015) Aquaporin 1 and 5 expression decreases during human intervertebral disc degeneration: Novel HIF-1-mediated regulation of aquaporins in NP cells, Oncotarget, 6(14), pp. 11945-11958.en
dc.identifier.pmid25844601
dc.identifier.doi10.18632/oncotarget.3631en
dc.identifier.urihttp://hdl.handle.net/2436/622346
dc.description.abstractObjectives of this study were to investigate whether AQP1 and AQP5 expression is altered during intervertebral disc degeneration and if hypoxia and HIF-1 regulate their expression in NP cells. AQP expression was measured in human tissues from different degenerative grades; regulation by hypoxia and HIF-1 was studied using promoter analysis and gain- and loss-of-function experiments. We show that both AQPs are expressed in the disc and that mRNA and protein levels decline with human disease severity. Bioinformatic analyses of AQP promoters showed multiple evolutionarily conserved HREs. Surprisingly, hypoxia failed to induce promoter activity or expression of either AQP. While genomic chromatin immunoprecipitation showed limited binding of HIF-1α to conserved HREs, their mutation did not suppress promoter activities. Stable HIF-1α suppression significantly decreased mRNA and protein levels of both AQPs, but HIF-1α failed to induce AQP levels following accumulation. Together, our results demonstrate that AQP1 and AQP5 expression is sensitive to human disc degeneration and that HIF-1α uniquely maintains basal expression of both AQPs in NP cells, independent of oxemic tension and HIF-1 binding to promoter HREs. Diminished HIF-1 activity during degeneration may suppress AQP levels in NP cells, compromising their ability to respond to extracellular osmolarity changes.en
dc.description.sponsorshipThis work is supported by grants from the National Institutes of Health AR055655, AR064733 and AR050087 (MVR). Zariel I. Johnson is supported by T32 AR052273.en
dc.formatapplication/PDFen
dc.languageeng
dc.language.isoenen
dc.publisherImpact Journalsen
dc.relation.urlhttp://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=3631&path[]=7417en
dc.rightsLicence for published version: Creative Commons Attribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAnimalsen
dc.subjectHumansen
dc.subjectRatsen
dc.subjectMicroscopy, Fluorescenceen
dc.subjectBlotting, Westernen
dc.subjectImmunohistochemistryen
dc.subjectChromatin Immunoprecipitationen
dc.subjectTransfectionen
dc.subjectCell Hypoxiaen
dc.subjectGene Expression Regulationen
dc.subjectResponse Elementsen
dc.subjectAquaporin 1en
dc.subjectAquaporin 5en
dc.subjectHypoxia-Inducible Factor 1, alpha Subuniten
dc.subjectReal-Time Polymerase Chain Reactionen
dc.subjectIntervertebral Disc Degenerationen
dc.titleAquaporin 1 and 5 expression decreases during human intervertebral disc degeneration: Novel HIF-1-mediated regulation of aquaporins in NP cellsen
dc.typeJournal articleen
dc.identifier.eissn1949-2553
dc.identifier.journalOncotargeten
dc.date.updated2019-05-09T13:37:52Z
dc.contributor.institutionDepartment of Orthopaedic Surgery and Graduate Program in Cell and Developmental Biology, Thomas Jefferson University, Philadelphia, PA, USA.
pubs.place-of-publicationUnited States
dc.date.accepted2015-03-05
rioxxterms.funderUniversity of Wolverhamptonen
rioxxterms.identifier.projectAR050087en
rioxxterms.identifier.projectAR055655en
rioxxterms.identifier.projectAR064733en
rioxxterms.identifier.projectT32 AR052273en
rioxxterms.identifier.projectR01 AR050087en
rioxxterms.identifier.projectR01 AR055655en
rioxxterms.identifier.projectR01 AR064733en
rioxxterms.identifier.projectP30 CA056036en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2019-05-13en
dc.source.volume6
dc.source.issue14
dc.source.beginpage11945
dc.source.endpage11958
dc.description.versionPublished version
refterms.dateFCD2019-05-13T11:39:34Z
refterms.versionFCDVoR
refterms.dateFOA2019-05-13T11:45:26Z


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Licence for published version: Creative Commons Attribution 4.0 International
Except where otherwise noted, this item's license is described as Licence for published version: Creative Commons Attribution 4.0 International