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Conference Paper: Inhibition of renin-angiotensin-aldosterone system abolishes polymeric-IgA induced TGF- synthesis by human mesangial cells in IgA nephropathy

TitleInhibition of renin-angiotensin-aldosterone system abolishes polymeric-IgA induced TGF- synthesis by human mesangial cells in IgA nephropathy
Authors
Issue Date2009
PublisherAmerican Society of Nephrology
Citation
Renal Week 2009 - The 2009 Annual Meeting of the American Society of Nephrology (ASN), San Diego, CA., 27 October-1 November 2009. In Renal Week 2009 Digital Abstract Book, 2009, p. 294A How to Cite?
AbstractThe renin-angiotensin system (RAS) is involved in the development of progressive renal fibrosis in IgA nephropathy (IgAN). We had previously shown that polymeric IgA (pIgA) from IgAN patients up-regulated TGF-β synthesis by cultured human mesangial cells (HMC) through up-regulation of local RAS. In the present study, we examined the role of aldosterone (Aldo) in pIgA-induced TGF-β synthesis by HMC. Constitutive expression of the major components of renin-angiotensin-aldosterone system (RAAS) which regulate the synthesis and action of Aldo, including mineralocorticoid receptor (MR), 11β-hydroxysteroid dehydrogenase type II (11β-HSD2) and aldosterone synthesis (CYP11B2), was demonstrated in HMC by real-time PCR and immunofluorescence staining. Polymeric IgA were purified from IgAN patients (n=28) and normal subjects (n=24) using affinity and size exclusion chromatography. Aldo synthesis and CYP11B2 expression in HMC were up-regulated by pIgA from IgAN patient in dose- and time dependent manner, but not by pIgA from healthy subjects. Exogenous angiotensin II (AngII) significantly increased the expression of AngII receptor subtype-I (ATR1), CYP11B2 and Aldo synthesis by HMC. The release of TGF-β by HMC was up-regulated dose-dependently when HMC were incubated with either AngII or Aldo. Interesting, further increase in TGF-β release was observed when HMC were cultured with both AngII and Aldo. Addition of Aldo to HMC up-regulated the expression of angiotensin converting enzyme, angiotensinogen and the release of AngII. The data suggest the presence of a vicious cycle between pIgA-induced AngII and Aldo in HMC. Pre-incubation of HMC with either losartan or eplererone only partially suppressed the pIgA-induced TGF-β release (< 40%), while combination of both inhibitors achieved more than 90% inhibition of TGF-β release. In conclusion, our in vitro data suggest that aldosterone also plays an important role in the pIgA-induced TGF-β synthesis in HMC. Specific RAAS blockade with aldosterone in combination with ATR1 blocker could effectively ameliorate pIgA-induced mesangial injury in IgAN.
DescriptionThursday Poster Session - Renal Experimental Pathology I: TH-PO795
Persistent Identifierhttp://hdl.handle.net/10722/126391

 

DC FieldValueLanguage
dc.contributor.authorLeung, JCKen_HK
dc.contributor.authorChan, LYYen_HK
dc.contributor.authorTam, KYen_HK
dc.contributor.authorTang, SCWen_HK
dc.contributor.authorLai, KNen_HK
dc.date.accessioned2010-10-31T12:25:57Z-
dc.date.available2010-10-31T12:25:57Z-
dc.date.issued2009en_HK
dc.identifier.citationRenal Week 2009 - The 2009 Annual Meeting of the American Society of Nephrology (ASN), San Diego, CA., 27 October-1 November 2009. In Renal Week 2009 Digital Abstract Book, 2009, p. 294Aen_HK
dc.identifier.urihttp://hdl.handle.net/10722/126391-
dc.descriptionThursday Poster Session - Renal Experimental Pathology I: TH-PO795-
dc.description.abstractThe renin-angiotensin system (RAS) is involved in the development of progressive renal fibrosis in IgA nephropathy (IgAN). We had previously shown that polymeric IgA (pIgA) from IgAN patients up-regulated TGF-β synthesis by cultured human mesangial cells (HMC) through up-regulation of local RAS. In the present study, we examined the role of aldosterone (Aldo) in pIgA-induced TGF-β synthesis by HMC. Constitutive expression of the major components of renin-angiotensin-aldosterone system (RAAS) which regulate the synthesis and action of Aldo, including mineralocorticoid receptor (MR), 11β-hydroxysteroid dehydrogenase type II (11β-HSD2) and aldosterone synthesis (CYP11B2), was demonstrated in HMC by real-time PCR and immunofluorescence staining. Polymeric IgA were purified from IgAN patients (n=28) and normal subjects (n=24) using affinity and size exclusion chromatography. Aldo synthesis and CYP11B2 expression in HMC were up-regulated by pIgA from IgAN patient in dose- and time dependent manner, but not by pIgA from healthy subjects. Exogenous angiotensin II (AngII) significantly increased the expression of AngII receptor subtype-I (ATR1), CYP11B2 and Aldo synthesis by HMC. The release of TGF-β by HMC was up-regulated dose-dependently when HMC were incubated with either AngII or Aldo. Interesting, further increase in TGF-β release was observed when HMC were cultured with both AngII and Aldo. Addition of Aldo to HMC up-regulated the expression of angiotensin converting enzyme, angiotensinogen and the release of AngII. The data suggest the presence of a vicious cycle between pIgA-induced AngII and Aldo in HMC. Pre-incubation of HMC with either losartan or eplererone only partially suppressed the pIgA-induced TGF-β release (< 40%), while combination of both inhibitors achieved more than 90% inhibition of TGF-β release. In conclusion, our in vitro data suggest that aldosterone also plays an important role in the pIgA-induced TGF-β synthesis in HMC. Specific RAAS blockade with aldosterone in combination with ATR1 blocker could effectively ameliorate pIgA-induced mesangial injury in IgAN.-
dc.languageengen_HK
dc.publisherAmerican Society of Nephrology-
dc.relation.ispartofRenal Week 2009 Digital Abstract Booken_HK
dc.titleInhibition of renin-angiotensin-aldosterone system abolishes polymeric-IgA induced TGF- synthesis by human mesangial cells in IgA nephropathyen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailLeung, JCK: jckleung@hku.hken_HK
dc.identifier.emailChan, LYY: yychanb@HKUCC.hku.hken_HK
dc.identifier.emailTam, KY: asura_cathy@yahoo.com.hken_HK
dc.identifier.emailTang, SCW: scwtang@hku.hk-
dc.identifier.emailLai, KN: knlai@hku.hk-
dc.identifier.authorityLeung, JCK=rp00448en_HK
dc.identifier.authorityTang, SCW=rp00480en_HK
dc.identifier.authorityLai, KN=rp00324en_HK
dc.identifier.hkuros174080en_HK
dc.identifier.spage294A-
dc.identifier.epage294A-
dc.description.otherRenal Week 2009 - The 2009 Annual Meeting of the American Society of Nephrology (ASN), San Diego, CA., 27 October-1 November 2009. In Renal Week 2009 Digital Abstract Book, 2009, p. 294A-

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