TGF-beta1 inhibits expression and activity of hENT1 in a nitric oxide-dependent manner in human umbilical vein endothelium

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dc.catalogadorgjm
dc.contributor.authorVega Pizarro, José Luis Eduardo
dc.contributor.authorPuebla Aracena, Carlos Alberto
dc.contributor.authorVásquez, Rodrigo
dc.contributor.authorFarías Jofré, Marcelo Enrique
dc.contributor.authorAlarcón, Julio
dc.contributor.authorPastor-Anglada, Marçal
dc.contributor.authorKrause Leyton, Bernardo
dc.contributor.authorCasanello Toledo, Paola Cecilia
dc.contributor.authorSobrevía Luarte, Luis Alberto
dc.date.accessioned2023-05-19T20:25:08Z
dc.date.available2023-05-19T20:25:08Z
dc.date.issued2009
dc.description.abstractAims: We studied whether transforming growth factor β1 (TGF-β1) modulates human equilibrative nucleoside transporters 1 (hENT1) expression and activity in human umbilical vein endothelial cells (HUVECs). hENT1-mediated adenosine transport and expression are reduced in gestational diabetes and hyperglycaemia, conditions associated with increased synthesis and release of nitric oxide (NO) and TGF-β1 in this cell type. TGF-β1 increases NO synthesis via activation of TGF-β receptor type II (TβRII), and NO inhibits hENT1 expression and activity in HUVECs. Methods and results: HUVECs (passage 2) were used for experiments. Total and hENT1-mediated adenosine transport was measured in the absence or presence of TGF-β1, NG-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor), S-nitroso-N-acetyl-L,D-penicillamine (SNAP, NO donor), and/or KT-5823 (protein kinase G inhibitor) in control cells and cells expressing a truncated form of TGF-β1 receptor type II (TTβRII). Western blot and real-time PCR were used to determine hENT1 protein abundance and mRNA expression. SLC29A1 gene promoter and specific protein 1 (Sp1) transcription factor activity was assayed. Vascular reactivity was assayed in endothelium-intact or -denuded umbilical vein rings. TGF-β1 reduced hENT1-mediated adenosine transport, hENT1 protein abundance, hENT1 mRNA expression, and SLC29A1 gene promoter activity, but increased Sp1 binding to DNA. TGF-β1 effect was blocked by L-NAME and KT-5823 and mimicked by SNAP in control cells. However, TGF-β1 was ineffective in cells expressing TTβRII or a mutated Sp1 consensus sequence. Vasodilatation in response to TGF-β1 and S-(4-nitrobenzyl)-6-thio-inosine (an ENT inhibitor) was endothelium-dependent and blocked by KT-5823 and ZM-241385. Conclusion: hENT1 is down-regulated by activation of TβRII by TGF-β1 in HUVECs, a phenomenon where NO and Sp1 play key roles. These findings comprise physiological mechanisms that could be important in diseases where TGF-β1 plasma level is increased as in gestational diabetic mothers or patients with diabetes mellitus.
dc.fechaingreso.objetodigital2023-07-14
dc.fuente.origenORCID
dc.identifier.doi10.1093/cvr/cvp045
dc.identifier.eissn1755-3245
dc.identifier.issn0008-6363
dc.identifier.pubmedidPMID: 19193655
dc.identifier.urihttps://doi.org/10.1093/cvr/cvp045
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/67287
dc.information.autorucFacultad de Ciencias Biológicas; Vega Pizarro, José Luis Eduardo; 0000-0001-9333-8729; 165832
dc.information.autorucFacultad de Ciencias Biológicas; Puebla Aracena, Carlos Alberto; 0000-0001-6648-2135; 124965
dc.information.autorucEscuela de Medicina; Farías Jofré, Marcelo Enrique; 0000-0003-0473-2295; 12286
dc.information.autorucEscuela de Medicina; Krause Leyton, Bernardo; 0000-0002-3563-6143; 1005678
dc.information.autorucEscuela de Medicina; Casanello Toledo, Paola Cecilia; 0000-0002-2355-1476; 146772
dc.information.autorucEscuela de Medicina; Sobrevía Luarte, Luis Alberto; 0000-0001-5802-2243; 1002656
dc.issue.numero3
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final467
dc.pagina.inicio458
dc.revistaCardiovascular Research
dc.rightsacceso restringido
dc.subjectTGF-β1es_ES
dc.subjectAdenosinees_ES
dc.subjectNitric oxidees_ES
dc.subjectEndotheliumes_ES
dc.subjectMembranees_ES
dc.subjectTransportes_ES
dc.subjectHumanes_ES
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleTGF-beta1 inhibits expression and activity of hENT1 in a nitric oxide-dependent manner in human umbilical vein endotheliumes_ES
dc.typeartículo
dc.volumen82
sipa.codpersvinculados165832
sipa.codpersvinculados124965
sipa.codpersvinculados12286
sipa.codpersvinculados1005678
sipa.codpersvinculados146772
sipa.codpersvinculados1002656
sipa.indexPubmed
sipa.trazabilidadORCID;14-07-2023
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