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Conference Paper: Anti-dsDNA antibodies induce epithelial-to-mesenchymal transition and fibrotic processes in human proximal renal tubular epithelial cells

TitleAnti-dsDNA antibodies induce epithelial-to-mesenchymal transition and fibrotic processes in human proximal renal tubular epithelial cells
Authors
Issue Date2012
PublisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org
Citation
The 2012 Annual Meeting and Scientific Exposition of the American Society of Nephrology (Kidney Week 2012), San Diego, CA., 30 October-4 November 2012. In Journal of the American Society of Nephrology, 2012, v. 23 abstract suppl., p. 338A, abstract TH-PO1034 How to Cite?
AbstractBACKGROUND: Tubulo-interstitial pathology predicts renal prognosis. We investigated the role of anti-dsDNA antibodies in the pathogenesis of tubulo-interstitial pathology in lupus nephritis, focusing on proximal renal tubular epithelial cells (PTEC) and epithelial-to-mesenchymal transition (EMT). METHODS: Female NZBWF1/J mice at different stages of nephritis were sacrificed and kidneys harvested to assess the tubulo-interstitial changes over time. Growth-arrested primary human PTEC were cultured with human polyclonal anti-dsDNA antibodies or control IgG (10μg/ml for both) for periods up to 48h, and investigated for the synthesis of mediators of fibrosis and EMT. RESULTS: NZBWF1/J mice showed progressive tubular damage over time, as denoted by tubular atrophy, protein cast deposition, mononuclear cell infiltration and increasing tubulo-interstitial expression of fibronectin, collagen type I and fibroblast specific protein-1 (FSP-1). Anti-dsDNA antibodies significantly induced the synthesis of soluble and insoluble fibronectin in PTEC after 24h incubation (P<0.01 for both). Anti-dsDNA antibodies induced FSP-1 and β-catenin synthesis (P<0.001 for both), which was accompanied by increased ERK and PKC-α phosphorylation. Inhibition of ERK and PKC-α activation using specific inhibitors reduced anti-dsDNA antibody induced EMT markers and fibronectin synthesis, and preserved normal PTEC phenotype. CONCLUSIONS: Our data demonstrate that anti-dsDNA antibodies contribute to tubulo-interstitial pathology in lupus nephritis via direct effects on PTEC which are mediated through ERK and PKC-α activation.
DescriptionMeeting Theme: Curing Kidney Disease
Session - Pathobiology: Extracellular Matrix Biology, Fibrosis, Cell Adhesion: abstract TH-PO1034
Persistent Identifierhttp://hdl.handle.net/10722/186840
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699

 

DC FieldValueLanguage
dc.contributor.authorHo, SSKen_US
dc.contributor.authorYung, Sen_US
dc.contributor.authorCheung, KFen_US
dc.contributor.authorTse, WWen_US
dc.contributor.authorChan, DTMen_US
dc.date.accessioned2013-08-20T12:21:13Z-
dc.date.available2013-08-20T12:21:13Z-
dc.date.issued2012en_US
dc.identifier.citationThe 2012 Annual Meeting and Scientific Exposition of the American Society of Nephrology (Kidney Week 2012), San Diego, CA., 30 October-4 November 2012. In Journal of the American Society of Nephrology, 2012, v. 23 abstract suppl., p. 338A, abstract TH-PO1034en_US
dc.identifier.issn1046-6673-
dc.identifier.urihttp://hdl.handle.net/10722/186840-
dc.descriptionMeeting Theme: Curing Kidney Disease-
dc.descriptionSession - Pathobiology: Extracellular Matrix Biology, Fibrosis, Cell Adhesion: abstract TH-PO1034-
dc.description.abstractBACKGROUND: Tubulo-interstitial pathology predicts renal prognosis. We investigated the role of anti-dsDNA antibodies in the pathogenesis of tubulo-interstitial pathology in lupus nephritis, focusing on proximal renal tubular epithelial cells (PTEC) and epithelial-to-mesenchymal transition (EMT). METHODS: Female NZBWF1/J mice at different stages of nephritis were sacrificed and kidneys harvested to assess the tubulo-interstitial changes over time. Growth-arrested primary human PTEC were cultured with human polyclonal anti-dsDNA antibodies or control IgG (10μg/ml for both) for periods up to 48h, and investigated for the synthesis of mediators of fibrosis and EMT. RESULTS: NZBWF1/J mice showed progressive tubular damage over time, as denoted by tubular atrophy, protein cast deposition, mononuclear cell infiltration and increasing tubulo-interstitial expression of fibronectin, collagen type I and fibroblast specific protein-1 (FSP-1). Anti-dsDNA antibodies significantly induced the synthesis of soluble and insoluble fibronectin in PTEC after 24h incubation (P<0.01 for both). Anti-dsDNA antibodies induced FSP-1 and β-catenin synthesis (P<0.001 for both), which was accompanied by increased ERK and PKC-α phosphorylation. Inhibition of ERK and PKC-α activation using specific inhibitors reduced anti-dsDNA antibody induced EMT markers and fibronectin synthesis, and preserved normal PTEC phenotype. CONCLUSIONS: Our data demonstrate that anti-dsDNA antibodies contribute to tubulo-interstitial pathology in lupus nephritis via direct effects on PTEC which are mediated through ERK and PKC-α activation.-
dc.languageengen_US
dc.publisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org-
dc.relation.ispartofJournal of the American Society of Nephrologyen_US
dc.titleAnti-dsDNA antibodies induce epithelial-to-mesenchymal transition and fibrotic processes in human proximal renal tubular epithelial cellsen_US
dc.typeConference_Paperen_US
dc.identifier.emailYung, S: ssyyung@hku.hken_US
dc.identifier.emailCheung, KF: skfc819@hku.hken_US
dc.identifier.emailTse, WW: kenniskt@hku.hken_US
dc.identifier.emailChan, DTM: dtmchan@hku.hken_US
dc.identifier.authorityYung, S=rp00455en_US
dc.identifier.authorityChan, DTM=rp00394en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros220417en_US
dc.identifier.volume23-
dc.identifier.issueabstract suppl.-
dc.identifier.spage338Aen_US
dc.identifier.epage338Aen_US
dc.publisher.placeUnited States-

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