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dc.contributor.authorLehmann, Guillermo L
dc.contributor.authorGinsberg, Michael
dc.contributor.authorNolan, Daniel J
dc.contributor.authorRodríguez, Cristina
dc.contributor.authorMartínez-González, José
dc.contributor.authorZeng, Shemin
dc.contributor.authorVoigt, Andrew P
dc.contributor.authorMullins, Robert F
dc.contributor.authorRafii, Shahin
dc.contributor.authorRodriguez-Boulan, Enrique
dc.contributor.authorBenedicto, Ignacio
dc.identifier.citationCells. 2022 Sep 24;11(19):2975es_ES
dc.description.abstractAlpha-2-macroglobulin (A2M) is a protease inhibitor that regulates extracellular matrix (ECM) stability and turnover. Here, we show that A2M is expressed by endothelial cells (ECs) from human eye choroid. We demonstrate that retinal pigment epithelium (RPE)-conditioned medium induces A2M expression specifically in ECs. Experiments using chemical inhibitors, blocking antibodies, and recombinant proteins revealed a key role of VEGF-A in RPE-mediated A2M induction in ECs. Furthermore, incubation of ECs with RPE-conditioned medium reduces matrix metalloproteinase-2 gelatinase activity of culture supernatants, which is partially restored after A2M knockdown in ECs. We propose that dysfunctional RPE or choroidal blood vessels, as observed in retinal diseases such as age-related macular degeneration, may disrupt the crosstalk mechanism we describe here leading to alterations in the homeostasis of choroidal ECM, Bruch's membrane and visual function.es_ES
dc.description.sponsorshipThis work was funded by grants EY08538 and GM34107 from NIH, award 2013-028 by the Tri-Institutional Stem Cell Initiative established by a grant from The Starr Foundation and by Departmental grants from Research to Prevent Blindness and Dyson Foundations (E.R.-B.). I.B. was supported by the Comunidad Autónoma de Madrid (grants 2017-T1/BMD-5247 and 2021-5A/BMD20944). The CNIC is supported by the Ministerio de Ciencia e Innovación (MCIN), the Instituto de Salud Carlos III, and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MCIN/AEI/10.13039/501100011033). R.F.M. and S.Z. were supported by grant EY024605 from NIH. J.M.-G. was supported by grant RTI2018-094727-B-100 funded by MCIN/AEI/10.13039/501100011033.es_ES
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI) es_ES
dc.subject.meshPregnancy-Associated alpha 2-Macroglobulins es_ES
dc.subject.meshRetinal Pigment Epithelium es_ES
dc.subject.meshAntibodies, Blocking es_ES
dc.subject.meshCulture Media, Conditioned es_ES
dc.subject.meshEndothelial Cells es_ES
dc.subject.meshFemale es_ES
dc.subject.meshGelatinases es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMatrix Metalloproteinase 2 es_ES
dc.subject.meshPregnancy es_ES
dc.subject.meshProtease Inhibitors es_ES
dc.subject.meshRecombinant Proteins es_ES
dc.subject.meshTranscription Factors es_ES
dc.subject.meshVascular Endothelial Growth Factor A es_ES
dc.titleRetinal Pigment Epithelium-Secreted VEGF-A Induces Alpha-2-Macroglobulin Expression in Endothelial Cells.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderComunidad de Madrid (España) es_ES
dc.contributor.funderInstituto de Salud Carlos III es_ES
dc.contributor.funderFundación ProCNIC es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España) es_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genéticaes_ES
dc.rights.accessRightsopen accesses_ES

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Atribución 4.0 Internacional
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