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Article: Polymeric IgA1 from Patients with IgA Nephropathy Upregulates Transforming Growth Factor-β Synthesis and Signal Transduction in Human Mesangial Cells via the Renin-Angiotensin System

TitlePolymeric IgA1 from Patients with IgA Nephropathy Upregulates Transforming Growth Factor-β Synthesis and Signal Transduction in Human Mesangial Cells via the Renin-Angiotensin System
Authors
Issue Date2003
PublisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org
Citation
Journal Of The American Society Of Nephrology, 2003, v. 14 n. 12, p. 3127-3137 How to Cite?
AbstractThe effects of polymeric IgA1 (pIgA1) and monomeric IgA1 (mIgA1) from patients with IgA nephropathy (IgAN) on the renin-angiotensin system (RAS) and TGF-β synthesis were examined in cultured human mesangial cells (HMC). Both pIgA1 and mIgA1 induced renin gene expression in HMC, in a dose-dependent manner. Similar findings were observed for TGF-β gene and protein expression. The values measured in HMC incubated with pIgA1 were significantly higher than those in HMC incubated with equivalent amounts of mIgA 1. When similar experiments were performed with the addition of either captopril or losartan, there was a significant increase in the renin gene expression by HMC, whereas the synthesis of TGF-β was markedly reduced. The TGF-β signal transduction pathways in HMC were studied by measuring the receptor-regulated Smad proteins (Smad 2 and 3) and common-partner Smad proteins (Smad 4). pIgA1 from patients with IgAN upregulated Smad activity in HMC, and the activity observed in HMC that had been preincubated with pIgA1 was readily suppressed with optimal concentrations of captopril or losartan. The effects of pIgA1 on the RAS were further examined in HMC incubated with IgA isolated from 30 patients with IgAN, 30 healthy subjects, and disease control subjects with other diseases. pIgA1 induction of angiotensin II or TGF-β synthesis in HMC was significantly greater with preparations from patients with IgAN, compared with healthy or disease control subjects. The findings support a pathogenetic role of pIgA1 in IgAN through upregulation of the RAS and TGF-β, leading to chronic renal failure with renal fibrosis.
Persistent Identifierhttp://hdl.handle.net/10722/162736
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLai, KNen_US
dc.contributor.authorTang, SCWen_US
dc.contributor.authorGuh, JYen_US
dc.contributor.authorChuang, TDen_US
dc.contributor.authorLam, MFen_US
dc.contributor.authorChan, LYYen_US
dc.contributor.authorTsang, AWLen_US
dc.contributor.authorLeung, JCKen_US
dc.date.accessioned2012-09-05T05:22:54Z-
dc.date.available2012-09-05T05:22:54Z-
dc.date.issued2003en_US
dc.identifier.citationJournal Of The American Society Of Nephrology, 2003, v. 14 n. 12, p. 3127-3137en_US
dc.identifier.issn1046-6673en_US
dc.identifier.urihttp://hdl.handle.net/10722/162736-
dc.description.abstractThe effects of polymeric IgA1 (pIgA1) and monomeric IgA1 (mIgA1) from patients with IgA nephropathy (IgAN) on the renin-angiotensin system (RAS) and TGF-β synthesis were examined in cultured human mesangial cells (HMC). Both pIgA1 and mIgA1 induced renin gene expression in HMC, in a dose-dependent manner. Similar findings were observed for TGF-β gene and protein expression. The values measured in HMC incubated with pIgA1 were significantly higher than those in HMC incubated with equivalent amounts of mIgA 1. When similar experiments were performed with the addition of either captopril or losartan, there was a significant increase in the renin gene expression by HMC, whereas the synthesis of TGF-β was markedly reduced. The TGF-β signal transduction pathways in HMC were studied by measuring the receptor-regulated Smad proteins (Smad 2 and 3) and common-partner Smad proteins (Smad 4). pIgA1 from patients with IgAN upregulated Smad activity in HMC, and the activity observed in HMC that had been preincubated with pIgA1 was readily suppressed with optimal concentrations of captopril or losartan. The effects of pIgA1 on the RAS were further examined in HMC incubated with IgA isolated from 30 patients with IgAN, 30 healthy subjects, and disease control subjects with other diseases. pIgA1 induction of angiotensin II or TGF-β synthesis in HMC was significantly greater with preparations from patients with IgAN, compared with healthy or disease control subjects. The findings support a pathogenetic role of pIgA1 in IgAN through upregulation of the RAS and TGF-β, leading to chronic renal failure with renal fibrosis.en_US
dc.languageengen_US
dc.publisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.orgen_US
dc.relation.ispartofJournal of the American Society of Nephrologyen_US
dc.subject.meshCaptopril - Administration & Dosageen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshGenes, Ras - Drug Effectsen_US
dc.subject.meshGlomerular Mesangium - Cytologyen_US
dc.subject.meshGlomerulonephritis, Igaen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunoglobulin Aen_US
dc.subject.meshLosartan - Administration & Dosageen_US
dc.subject.meshRna, Messenger - Biosynthesisen_US
dc.subject.meshRenin - Geneticsen_US
dc.subject.meshRenin-Angiotensin System - Physiologyen_US
dc.subject.meshSignal Transduction - Drug Effectsen_US
dc.subject.meshTransforming Growth Factor Beta - Biosynthesis - Genetics - Physiologyen_US
dc.subject.meshUp-Regulationen_US
dc.titlePolymeric IgA1 from Patients with IgA Nephropathy Upregulates Transforming Growth Factor-β Synthesis and Signal Transduction in Human Mesangial Cells via the Renin-Angiotensin Systemen_US
dc.typeArticleen_US
dc.identifier.emailLai, KN:knlai@hku.hken_US
dc.identifier.emailTang, SCW:scwtang@hku.hken_US
dc.identifier.emailLeung, JCK:jckleung@hku.hken_US
dc.identifier.authorityLai, KN=rp00324en_US
dc.identifier.authorityTang, SCW=rp00480en_US
dc.identifier.authorityLeung, JCK=rp00448en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1097/01.ASN.0000095639.56212.BFen_US
dc.identifier.pmid14638911-
dc.identifier.scopuseid_2-s2.0-0344667757en_US
dc.identifier.hkuros87423-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0344667757&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume14en_US
dc.identifier.issue12en_US
dc.identifier.spage3127en_US
dc.identifier.epage3137en_US
dc.identifier.isiWOS:000186761700013-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLai, KN=7402135706en_US
dc.identifier.scopusauthoridTang, SCW=7403437082en_US
dc.identifier.scopusauthoridGuh, JY=7005320637en_US
dc.identifier.scopusauthoridChuang, TD=7202737751en_US
dc.identifier.scopusauthoridLam, MF=7202630163en_US
dc.identifier.scopusauthoridChan, LYY=8108378300en_US
dc.identifier.scopusauthoridTsang, AWL=7006979244en_US
dc.identifier.scopusauthoridLeung, JCK=7202180349en_US

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