Role of chymase in diabetic nephropathy

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dc.contributor.authorCristovam, Priscila C. [UNIFESP]
dc.contributor.authorCarmona, Adriana K. [UNIFESP]
dc.contributor.authorArnoni, Carine P. [UNIFESP]
dc.contributor.authorMaquigussa, Edgar [UNIFESP]
dc.contributor.authorPereira, Luciana G. [UNIFESP]
dc.contributor.authorBoim, Mirian A. [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:27:33Z
dc.date.available2016-01-24T14:27:33Z
dc.date.issued2012-08-01
dc.description.abstractChymase is an alternative pathway for angiotensin-converting enzyme in angiotensin II (Ang II) formation, and its expression is increased in human diabetic kidneys and in human mesangial cells (MCs) stimulated with high glucose. in addition, chymase activates transforming growth factor (TGF-beta 1) via an Ang II-independent pathway. the aim of this study was to evaluate the role of chymase on TGF-beta 1 activation in diabetic rats and in rat MCs (RMCs) stimulated with high glucose (HG). Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg, intravenous). After 30 (D30) or 60 (D60) days, chymase activity and the expression of profibrotic markers were evaluated. RMCs were stimulated with HG in the presence or absence of 50 mu mol/L chymostatin, a chymase inhibitor, or 100 nmol/L of losartan, an Ang II antagonist. Chymase activity and expression increased in 060 kidneys, with increased expression of fibronectin, type I and III collagen, TGF-beta 1 and Smad 3 and with no change in Smad 7 expression. RMCs exposed to HG presented increases in chymase activity and expression, together with upregulation in fibrosis markers and in the TGF-beta 1 signaling pathway. All these effects were reversed by chymostatin and by losartan, but type 1 angiotensin II receptor blockade did not interfere with the Smad 3 and 7 pathway. Similar to HG-stimulated RMCs, control RMCs treated with chymase responded with increased expression of TGF-beta 1, Smad 3 and fibrosis markers. These effects were reversed by chymostatin but not by losartan. the results indicate an important role for chymase in inducing fibrosis through TGF-beta 1 activation, parallel with Ang II effects.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, BR-04023900 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Med, Renal Div, BR-04023900 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, BR-04023900 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Med, Renal Div, BR-04023900 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.sponsorshipFundacao Oswaldo Ramos (FOR)
dc.description.sponsorshipFundo de Auxilio aos Docentes e Alunos (FADA)
dc.format.extent985-992
dc.identifierhttp://dx.doi.org/10.1258/ebm.2012.011356
dc.identifier.citationExperimental Biology and Medicine. London: Royal Soc Medicine Press Ltd, v. 237, n. 8, p. 985-992, 2012.
dc.identifier.doi10.1258/ebm.2012.011356
dc.identifier.issn1535-3702
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/35160
dc.identifier.wosWOS:000309303400013
dc.language.isoeng
dc.publisherRoyal Soc Medicine Press Ltd
dc.relation.ispartofExperimental Biology and Medicine
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectchymaseen
dc.subjectchymostatinen
dc.subjectmesangial cellsen
dc.subjectdiabetic nephropathyen
dc.subjectTGF-beta 1en
dc.titleRole of chymase in diabetic nephropathyen
dc.typeinfo:eu-repo/semantics/article
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