MXRA5 is a TGF-β1-regulated human protein with anti-inflammatory and anti-fibrotic properties

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dc.contributor.author Poveda, Jonay
dc.contributor.author Sanz, Ana Belén
dc.contributor.author Fernández-Fernández, Beatriz
dc.contributor.author Carrasco, Susana
dc.contributor.author Ruiz-Ortega, Marta
dc.contributor.other UAM. Departamento de Anatomía Patológica es_ES
dc.contributor.other UAM. Departamento de Medicina es_ES
dc.contributor.other Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD) es_ES
dc.date.accessioned 2017-04-26T15:22:15Z
dc.date.available 2017-04-26T15:22:15Z
dc.date.issued 2017-01-01
dc.identifier.citation Journal of Cellular and Molecular Medicine 21.1 (2017): 154-164 en_US
dc.identifier.issn 1582-1838 (print) es_ES
dc.identifier.issn 1582-4934 (online) es_ES
dc.identifier.uri http://hdl.handle.net/10486/678037
dc.description.abstract Current therapy for chronic kidney disease (CKD) is unsatisfactory because of an insufficient understanding of its pathogenesis. Matrix remodelling-associated protein 5 (MXRA5, adlican) is a human protein of unknown function with high kidney tissue expression, not present in rodents. Given the increased expression of MXRA5 in injured tissues, including the kidneys, we have suggested that MXRA5 may modulate kidney injury. MXRA5 immunoreactivity was observed in tubular cells in human renal biopsies and in urine from CKD patients. We then explored factors regulating MXRA5 expression and MXRA5 function in cultured human proximal tubular epithelial cells and explored MXRA5 expression in kidney cancer cells and kidney tissue. The fibrogenic cytokine transforming growth factor-β1 (TGFβ1) up-regulated MXRA5 mRNA and protein expression. TGFβ1-induced MXRA5 up-regulation was prevented by either interference with TGFβ1 activation of the TGFβ receptor 1 (TGFBR1, ALK5) or by the vitamin D receptor agonist paricalcitol. By contrast, the pro-inflammatory cytokine TWEAK did not modulate MXRA5 expression. MXRA5 siRNA-induced down-regulation of constitutive MXRA5 expression resulted in higher TWEAK-induced expression of chemokines. In addition, MXRA5 down-regulation resulted in a magnified expression of genes encoding extracellular matrix proteins in response to TGFβ1. Furthermore, in clear cell renal cancer, von Hippel–Lindau (VHL) regulated MXRA5 expression. In conclusion, MXRA5 is a TGFβ1- and VHL-regulated protein and, for the first time, we identify MXRA5 functions as an anti-inflammatory and anti-fibrotic molecule. This information may yield clues to design novel therapeutic strategies in diseases characterized by inflammation and fibrosis. en_US
dc.description.sponsorship This work was supported by grants from the Instituto de Salud Carlos III (FEDER funds ISCIII RETIC REDINREN RD12/0021, PI13/00047, PI15/00298, PIE13/00051, Comunidad de Madrid (CIFRA S2010/BMD-2378), Sociedad Española de Nefrología. Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM) to AO, ISCIII Joan Rodes JR14/00028 to BFF and Miguel Servet MS12/03262, MS14/00133, MECD to JP, and Biobanco IIS-FJD PT13/0010/0012 en_US
dc.format.extent 11 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso eng es_ES
dc.publisher John Wiley & Sons Ltd. en_US
dc.publisher Foundation for Cellular and Molecular Medicine en_US
dc.relation.ispartof Journal of Cellular and Molecular Medicine en_US
dc.rights © 2016 The Authors en_US
dc.subject.other Adlican en_US
dc.subject.other Chronic kidney disease en_US
dc.subject.other Fibrosis en_US
dc.subject.other Inflammation en_US
dc.subject.other Kidney en_US
dc.subject.other Perlecan en_US
dc.subject.other Polycystic kidney disease en_US
dc.title MXRA5 is a TGF-β1-regulated human protein with anti-inflammatory and anti-fibrotic properties en_US
dc.type article en
dc.subject.eciencia Medicina es_ES
dc.relation.publisherversion http://dx.doi.org/10.1111/jcmm.12953 es_ES
dc.identifier.doi 10.1111/jcmm.12953 es_ES
dc.identifier.publicationfirstpage 154 es_ES
dc.identifier.publicationissue 1 es_ES
dc.identifier.publicationlastpage 164 es_ES
dc.identifier.publicationvolume 21 es_ES
dc.relation.projectID Comunidad de Madrid. S2010/BMD-2378/CIFRA es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento es_ES
dc.rights.accessRights openAccess en
dc.authorUAM Poveda Núñez, Jonay (264479)


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