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Conference Paper: Anti-dsDNA antibodies induce cell activation and fibronectin synthesis in human renal proximal tubular epithelial cells

TitleAnti-dsDNA antibodies induce cell activation and fibronectin synthesis in human renal proximal tubular epithelial cells
Authors
Issue Date2013
PublisherThe International Society of Nephrology (ISN),.
Citation
World Congress of Nephrology (WCN), Hong Kong, China, 31 May-4 June 2013, abstract no. SA012 How to Cite?
AbstractINTRODUCTION AND AIMS: Tubulo-interstitial inflammation and fibrosis correlate with renal prognosis. We investigated the role of anti-dsDNA antibodies in the pathogenesis of tubulo-interstitial pathology in lupus nephritis, focusing on their effect on epithelial-to-mesenchymal transition (EMT) and fibrogenesis in renal proximal tubular epithelial cells (PTEC). METHODS: Polyclonal anti-dsDNA antibodies were isolated from the sera of 10 patients with lupus nephritis using affinity chromatography. Confluent, growth-arrested human PTEC were cultured with human polyclonal anti-dsDNA antibodies or control IgG (10 μg/ml for both) for periods up to 48h and synthesis of mediators of cell activation, EMT and fibrosis investigated. RESULTS: Anti-dsDNA antibodies significantly induced synthesis of soluble and insoluble fibronectin in PTEC after 24h incubation (P<0.01 for both). Anti-dsDNA antibodies induced fibroblast specific protein-1 and β-catenin synthesis (P<0.001 for both), which was accompanied by increased ERK, p38 MAPK and PKC-α phosphorylation. Inhibition of ERK, p38 MAPK and PKC-α activation using PD98059, SB203580 and Go6976 respectively preserved normal PTEC phenotype and reduced anti-dsDNA antibody-induced EMT markers and fibronectin synthesis. CONCLUSIONS: Our data demonstrate that human polyclonal anti-dsDNA antibodies can induce the EMT cascade and fibronectin synthesis in PTEC through activation of MAPK and PKC pathways, thereby contributing to amplification of matrix protein deposition within the tubulo-interstitium during pathogenesis of lupus nephritis.
DescriptionConferenc theme: Sustainability and Diversity
Moderated Poster Session: Cell Signaling, Cell Growth Control, Hormones and Cytokines
Persistent Identifierhttp://hdl.handle.net/10722/186841

 

DC FieldValueLanguage
dc.contributor.authorYung, SSYen_US
dc.contributor.authorHo, SKen_US
dc.contributor.authorCheung, KFen_US
dc.contributor.authorChan, DTMen_US
dc.date.accessioned2013-08-20T12:21:13Z-
dc.date.available2013-08-20T12:21:13Z-
dc.date.issued2013en_US
dc.identifier.citationWorld Congress of Nephrology (WCN), Hong Kong, China, 31 May-4 June 2013, abstract no. SA012en_US
dc.identifier.urihttp://hdl.handle.net/10722/186841-
dc.descriptionConferenc theme: Sustainability and Diversity-
dc.descriptionModerated Poster Session: Cell Signaling, Cell Growth Control, Hormones and Cytokines-
dc.description.abstractINTRODUCTION AND AIMS: Tubulo-interstitial inflammation and fibrosis correlate with renal prognosis. We investigated the role of anti-dsDNA antibodies in the pathogenesis of tubulo-interstitial pathology in lupus nephritis, focusing on their effect on epithelial-to-mesenchymal transition (EMT) and fibrogenesis in renal proximal tubular epithelial cells (PTEC). METHODS: Polyclonal anti-dsDNA antibodies were isolated from the sera of 10 patients with lupus nephritis using affinity chromatography. Confluent, growth-arrested human PTEC were cultured with human polyclonal anti-dsDNA antibodies or control IgG (10 μg/ml for both) for periods up to 48h and synthesis of mediators of cell activation, EMT and fibrosis investigated. RESULTS: Anti-dsDNA antibodies significantly induced synthesis of soluble and insoluble fibronectin in PTEC after 24h incubation (P<0.01 for both). Anti-dsDNA antibodies induced fibroblast specific protein-1 and β-catenin synthesis (P<0.001 for both), which was accompanied by increased ERK, p38 MAPK and PKC-α phosphorylation. Inhibition of ERK, p38 MAPK and PKC-α activation using PD98059, SB203580 and Go6976 respectively preserved normal PTEC phenotype and reduced anti-dsDNA antibody-induced EMT markers and fibronectin synthesis. CONCLUSIONS: Our data demonstrate that human polyclonal anti-dsDNA antibodies can induce the EMT cascade and fibronectin synthesis in PTEC through activation of MAPK and PKC pathways, thereby contributing to amplification of matrix protein deposition within the tubulo-interstitium during pathogenesis of lupus nephritis.-
dc.languageengen_US
dc.publisherThe International Society of Nephrology (ISN),.-
dc.relation.ispartofWorld Congress of Nephrology (WCN)en_US
dc.titleAnti-dsDNA antibodies induce cell activation and fibronectin synthesis in human renal proximal tubular epithelial cellsen_US
dc.typeConference_Paperen_US
dc.identifier.emailYung, SSY: ssyyung@hku.hken_US
dc.identifier.emailCheung, KF: skfc819@hku.hken_US
dc.identifier.emailChan, DTM: dtmchan@hku.hken_US
dc.identifier.authorityYung, SSY=rp00455en_US
dc.identifier.authorityChan, DTM=rp00394en_US
dc.identifier.hkuros220418en_US
dc.publisher.placeBelgium-

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