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dc.contributor.authorNovoyatleva, Tatyana
dc.contributor.authorRai, Nabham
dc.contributor.authorKojonazarov, Baktybek
dc.contributor.authorVeeroju, Swathi
dc.contributor.authorBen-Batalla, Isabel
dc.contributor.authorCaruso, Paola
dc.contributor.authorShihan, Mazen
dc.contributor.authorPresser, Nadine
dc.contributor.authorGötz, Elsa
dc.contributor.authorLepper, Carina
dc.contributor.authorHerpel, Sebastian
dc.contributor.authorManaud, Grégoire
dc.contributor.authorPerros, Frédéric
dc.contributor.authorGall, Henning
dc.contributor.authorGhofrani, Hossein Ardeschir
dc.contributor.authorWeissmann, Norbert
dc.contributor.authorGrimminger, Friedrich
dc.contributor.authorWharton, John
dc.contributor.authorWilkins, Martin
dc.contributor.authorUpton, Paul
dc.contributor.authorLoges, Sonja
dc.contributor.authorMorrell, Nicholas
dc.contributor.authorSeeger, Werner
dc.contributor.authorSchermuly, Ralph T
dc.date.accessioned2022-01-28T16:40:30Z
dc.date.available2022-01-28T16:40:30Z
dc.date.issued2021-08-24
dc.date.submitted2020-08-26
dc.identifier.issn2399-3642
dc.identifier.others42003-021-02531-1
dc.identifier.other2531
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/333222
dc.description.abstractPulmonary arterial hypertension (PAH), is a fatal disease characterized by a pseudo-malignant phenotype. We investigated the expression and the role of the receptor tyrosine kinase Axl in experimental (i.e., monocrotaline and Su5416/hypoxia treated rats) and clinical PAH. In vitro Axl inhibition by R428 and Axl knock-down inhibited growth factor-driven proliferation and migration of non-PAH and PAH PASMCs. Conversely, Axl overexpression conferred a growth advantage. Axl declined in PAECs of PAH patients. Axl blockage inhibited BMP9 signaling and increased PAEC apoptosis, while BMP9 induced Axl phosphorylation. Gas6 induced SMAD1/5/8 phosphorylation and ID1/ID2 increase were blunted by BMP signaling obstruction. Axl association with BMPR2 was facilitated by Gas6/BMP9 stimulation and diminished by R428. In vivo R428 aggravated right ventricular hypertrophy and dysfunction, abrogated BMPR2 signaling, elevated pulmonary endothelial cell apoptosis and loss. Together, Axl is a key regulator of endothelial BMPR2 signaling and potential determinant of PAH.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/80/86/2368
dc.subject/631/80/82/23
dc.subject/631/443/592/1540
dc.subject/38/77
dc.subject/38/109
dc.subject/14/63
dc.subject/13/2
dc.subject/96/95
dc.subject/13/51
dc.subjectarticle
dc.titleDeficiency of Axl aggravates pulmonary arterial hypertension via BMPR2.
dc.typeArticle
dc.date.updated2022-01-28T16:40:29Z
prism.issueIdentifier1
prism.publicationNameCommun Biol
prism.volume4
dc.identifier.doi10.17863/CAM.80645
dcterms.dateAccepted2021-08-05
rioxxterms.versionofrecord10.1038/s42003-021-02531-1
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidNovoyatleva, Tatyana [0000-0002-3367-9940]
dc.contributor.orcidCaruso, Paola [0000-0002-3071-1917]
dc.contributor.orcidPerros, Frédéric [0000-0001-7730-2427]
dc.contributor.orcidGall, Henning [0000-0001-7016-7373]
dc.contributor.orcidGhofrani, Hossein Ardeschir [0000-0002-2029-4419]
dc.contributor.orcidGrimminger, Friedrich [0000-0001-8725-6276]
dc.contributor.orcidWharton, John [0000-0001-8110-2575]
dc.contributor.orcidWilkins, Martin [0000-0003-3926-1171]
dc.contributor.orcidUpton, Paul [0000-0003-2716-4921]
dc.contributor.orcidMorrell, Nicholas [0000-0001-5700-9792]
dc.contributor.orcidSeeger, Werner [0000-0003-1946-0894]
dc.contributor.orcidSchermuly, Ralph T [0000-0002-5167-6970]
dc.identifier.eissn2399-3642
pubs.funder-project-idDeutsche Forschungsgemeinschaft (German Research Foundation) (268555672, 268555672)
cam.issuedOnline2021-08-24


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