Activation of platelet-activating factor receptor exacerbates renal inflammation and promotes fibrosis

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dc.contributor.authorCorrea-Costa, Matheus
dc.contributor.authorAndrade-Oliveira, Vinicius
dc.contributor.authorBraga, Tarcio T.
dc.contributor.authorCastoldi, Angela
dc.contributor.authorAguiar, Cristhiane F.
dc.contributor.authorOrigassa, Clarice Silva Taemi [UNIFESP]
dc.contributor.authorRodas, Andrea C. D.
dc.contributor.authorHiyane, Meire I.
dc.contributor.authorMalheiros, Denise M. A. C.
dc.contributor.authorRios, Francisco J. O.
dc.contributor.authorJancar, Sonia
dc.contributor.authorCamara, Niels O. S. [UNIFESP]
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Glasgow
dc.date.accessioned2016-01-24T14:35:29Z
dc.date.available2016-01-24T14:35:29Z
dc.date.issued2014-04-01
dc.description.abstractPlatelet-activating factor (PAF) is a lipid mediator with important pro-inflammatory effects, being synthesized by several cell types including kidney cells. Although there is evidence of its involvement in acute renal dysfunction, its role in progressive kidney injury is not completely known. in the present study, we investigated the role of PAF receptor (PAFR) in an experimental model of chronic renal disease. Wild-type (WT) and PAFR knockout (KO) mice underwent unilateral ureter obstruction (UUO), and at kill time, urine and kidney tissue was collected. PAFR KO animals compared with WT mice present: (a) less renal dysfunction, evaluated by urine protein/creatinine ratio; (b) less fibrosis evaluated by collagen deposition, type I collagen, Lysyl Oxidase-1 (LOX-1) and transforming growth factor beta (TGF-beta) gene expression, and higher expression of bone morphogenetic protein 7 (BMP-7) (3.3-fold lower TGF-beta/BMP-7 ratio); (c) downregulation of extracellular matrix (ECM) and adhesion molecule-related machinery genes; and (d) lower levels of pro-inflammatory cytokines. These indicate that PAFR engagement by PAF or PAF-like molecules generated during UUO potentiates renal dysfunction and fibrosis and might promote epithelial-to-mesenchymal transition (EMT). Also, early blockade of PAFR after UUO leads to a protective effect, with less fibrosis deposition. in conclusion, PAFR signaling contributes to a pro-inflammatory environment in the model of obstructive nephropathy, favoring the fibrotic process, which lately will generate renal dysfunction and progressive organ failure.en
dc.description.affiliationUniv São Paulo, Inst Biomed Sci 4, Dept Immunol, BR-05508900 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Div Nephrol, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Fac Med, Dept Pathol, BR-05508900 São Paulo, Brazil
dc.description.affiliationUniv Glasgow, Inst Cardiovasc & Med Sci, Glasgow Cardiovasc Res Ctr, British Heart Fdn, Glasgow, Lanark, Scotland
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Div Nephrol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipInstituto Nacional de Ciencia e Tecnologia de Fluidos Complexos (INCT Complex Fluids)
dc.description.sponsorshipIDFAPESP: 2009/54474-8
dc.description.sponsorshipIDFAPESP: 2012/02270-2
dc.format.extent455-466
dc.identifierhttp://dx.doi.org/10.1038/labinvest.2013.155
dc.identifier.citationLaboratory Investigation. New York: Nature Publishing Group, v. 94, n. 4, p. 455-466, 2014.
dc.identifier.doi10.1038/labinvest.2013.155
dc.identifier.issn0023-6837
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/37571
dc.identifier.wosWOS:000333574900009
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofLaboratory Investigation
dc.rightsAcesso aberto
dc.subjectchronic kidney diseaseen
dc.subjectplatelet activating factor receptoren
dc.subjectrenal fibrosisen
dc.subjectrenal inflammationen
dc.titleActivation of platelet-activating factor receptor exacerbates renal inflammation and promotes fibrosisen
dc.typeArtigo
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