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dc.contributor.authorWalker, David J.
dc.contributor.authorLand, Stephen C.
dc.date.accessioned2018-04-13T08:30:08Z
dc.date.available2018-04-13T08:30:08Z
dc.date.issued2018-10
dc.identifier252808599
dc.identifier8aa491fe-6113-4cf2-959a-ef5b367f8f7f
dc.identifier85044646723
dc.identifier000440775700014
dc.identifier.citationWalker , D J & Land , S C 2018 , ' Regulation of vascular signalling by nuclear Sprouty2 in fetal lung epithelial cells : implications for co-ordinated airway and vascular branching in lung development ' , Comparative Biochemistry and Physiology Part - B: Biochemistry and Molecular Biology , vol. 224 , pp. 105-114 . https://doi.org/10.1016/j.cbpb.2018.01.007en
dc.identifier.issn1096-4959
dc.identifier.urihttps://hdl.handle.net/10023/13130
dc.descriptionThis work was supported by a Wellcome Trust project grant 088032/Z/08/Z to SCL.en
dc.description.abstractSprouty2 (Spry2) acts as a central regulator of tubular growth and branch patterning in the developing mammalian lung by controlling both magnitude and duration of growth factor signalling. To determine if this protein coordinates airway and vascular growth factor signalling, we tested the hypothesis that Spry2 links the primary cue for airway outgrowth, fibroblast growth factor-10 (FGF-10), to genomic events underpinning the expression and release of vascular endothelial growth factor-A (VEGF-A). Using primary fetal distal lung epithelial cells (FDLE) from rat, and immortalised human bronchial epithelial cells (16HBE14o-), we identified a nuclear sub-population of Spry2 which interacted with regions of the rat and human VEGF-A promoter spanning the hypoxia response element (HRE) and adjacent 3′ sites. In FDLE cultured at the PO2 of the fetal lung, FGF-10 relieved the Spry2 interaction at the HRE region by promoting clearance of a 39 kDa form and this was accompanied by histone-3 S10K14 phosphoacetylation, promoter de-methylation, hypoxia inducible factor-1α activation and VEGF-A expression. This repressive characteristic of nuclear Spry2 was relieved in 16HBE14o- by shRNA knockdown, and stable expression of mutants (C218A; C221A) that do not interact with the VEGF-A promoter HRE region. We conclude that nuclear Spry2 acts as a molecular link which co-ordinates airway and vascular growth of the cardiopulmonary system. This identifies Spry2 as a contributing determinant of design optimality in the mammalian lung.
dc.format.extent10
dc.format.extent2301898
dc.language.isoeng
dc.relation.ispartofComparative Biochemistry and Physiology Part - B: Biochemistry and Molecular Biologyen
dc.subjectCardio-pulmonary systemen
dc.subjectFibroblast growth factor-10en
dc.subjectGas exchangeen
dc.subjectHypoxia inducible factoren
dc.subjectLung developmenten
dc.subjectSymmorphosisen
dc.subjectQH301 Biologyen
dc.subjectQP Physiologyen
dc.subjectBiochemistryen
dc.subjectPhysiologyen
dc.subjectMolecular Biologyen
dc.subjectNDASen
dc.subject.lccQH301en
dc.subject.lccQPen
dc.titleRegulation of vascular signalling by nuclear Sprouty2 in fetal lung epithelial cells : implications for co-ordinated airway and vascular branching in lung developmenten
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. School of Psychology and Neuroscienceen
dc.identifier.doi10.1016/j.cbpb.2018.01.007
dc.description.statusPeer revieweden


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