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Article: Oxidative damages in tubular epithelial cells in IgA nephropathy: role of crosstalk between angiotensin II and aldosterone

TitleOxidative damages in tubular epithelial cells in IgA nephropathy: role of crosstalk between angiotensin II and aldosterone
Authors
Issue Date2011
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.translational-medicine.com/home/
Citation
Journal of Translational Medicine, 2011, v. 9 n. 1, article no. 169 How to Cite?
AbstractBACKGROUND: Inhibition of the renin-angiotensin-aldosterone system (RAAS) slows down the progression of chronic renal diseases (CKD) including IgA nephropathy (IgAN). Herein, we studied the pathogenetic roles of aldosterone (Aldo) in IgAN. METHODS: Human mesangial cells (HMC) was activated with polymeric IgA (pIgA) from IgAN patients and the effects on the expression of RAAS components and TGF-beta synthesis examined. To study the roles of RAAS in the glomerulotubular communication, proximal tubular epithelial cells (PTEC) was cultured with conditioned medium from pIgA-activated HMC with eplerenone or PD123319, the associated apoptotic event was measured by the generation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and reactive oxygen species (ROS). RESULTS: Polymeric IgA up-regulated the Aldo synthesis and aldosterone synthase expression by HMC. The release of TGF-beta by HMC was up-regulated synergistically by AngII and Aldo and this was inhibited by incubation of HMC with losartan plus eplerenone. Cultured PTEC express the mineralocorticoid receptor, but not synthesizing aldosterone. Apoptosis, demonstrated by cleaved PARP expression and caspase 3 activity, was induced in PTEC activated by conditioned medium prepared from HMC cultured with pIgA from IgAN patients. This apoptotic event was associated with increased generation of NADPH oxidase and ROS. Pre-incubation of PTEC with PD123319 and eplerenone achieved complete inhibition of PTEC apoptosis. CONCLUSIONS: Our data suggest that AngII and Aldo, released by pIgA activated HMC, served as mediators for inducing apoptosis of PTEC in glomerulo-tubular communications. Crosstalk between AngII and Aldo could participate in determining the tubular pathology of IgAN.
Persistent Identifierhttp://hdl.handle.net/10722/163403
ISSN
2015 Impact Factor: 3.694
2015 SCImago Journal Rankings: 1.766
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLeung, JCKen_US
dc.contributor.authorChan, LYYen_US
dc.contributor.authorTang, SCWen_US
dc.contributor.authorLam, MFen_US
dc.contributor.authorChow, CWen_US
dc.contributor.authorLim, AIen_US
dc.contributor.authorLai, KNen_US
dc.date.accessioned2012-09-05T05:30:56Z-
dc.date.available2012-09-05T05:30:56Z-
dc.date.issued2011en_US
dc.identifier.citationJournal of Translational Medicine, 2011, v. 9 n. 1, article no. 169en_US
dc.identifier.issn1479-5876en_US
dc.identifier.urihttp://hdl.handle.net/10722/163403-
dc.description.abstractBACKGROUND: Inhibition of the renin-angiotensin-aldosterone system (RAAS) slows down the progression of chronic renal diseases (CKD) including IgA nephropathy (IgAN). Herein, we studied the pathogenetic roles of aldosterone (Aldo) in IgAN. METHODS: Human mesangial cells (HMC) was activated with polymeric IgA (pIgA) from IgAN patients and the effects on the expression of RAAS components and TGF-beta synthesis examined. To study the roles of RAAS in the glomerulotubular communication, proximal tubular epithelial cells (PTEC) was cultured with conditioned medium from pIgA-activated HMC with eplerenone or PD123319, the associated apoptotic event was measured by the generation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and reactive oxygen species (ROS). RESULTS: Polymeric IgA up-regulated the Aldo synthesis and aldosterone synthase expression by HMC. The release of TGF-beta by HMC was up-regulated synergistically by AngII and Aldo and this was inhibited by incubation of HMC with losartan plus eplerenone. Cultured PTEC express the mineralocorticoid receptor, but not synthesizing aldosterone. Apoptosis, demonstrated by cleaved PARP expression and caspase 3 activity, was induced in PTEC activated by conditioned medium prepared from HMC cultured with pIgA from IgAN patients. This apoptotic event was associated with increased generation of NADPH oxidase and ROS. Pre-incubation of PTEC with PD123319 and eplerenone achieved complete inhibition of PTEC apoptosis. CONCLUSIONS: Our data suggest that AngII and Aldo, released by pIgA activated HMC, served as mediators for inducing apoptosis of PTEC in glomerulo-tubular communications. Crosstalk between AngII and Aldo could participate in determining the tubular pathology of IgAN.en_US
dc.languageengen_US
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.translational-medicine.com/home/en_US
dc.relation.ispartofJournal of Translational Medicineen_US
dc.rightsJournal of Translational Medicine. Copyright © BioMed Central Ltd.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAldosterone - pharmacology-
dc.subject.meshAngiotensin II - pharmacology - secretion-
dc.subject.meshEpithelial Cells - drug effects - enzymology - pathology-
dc.subject.meshGlomerulonephritis, IGA - enzymology - pathology-
dc.subject.meshKidney Tubules, Proximal - pathology-
dc.titleOxidative damages in tubular epithelial cells in IgA nephropathy: role of crosstalk between angiotensin II and aldosteroneen_US
dc.typeArticleen_US
dc.identifier.emailLeung, JCK: jckleung@hku.hken_US
dc.identifier.emailChan, LYY: yychanb@hkucc.hku.hken_US
dc.identifier.emailTang, SCW: scwtang@hku.hken_US
dc.identifier.emailLam, MF: feimflam@hku.hk-
dc.identifier.emailLai, KN: knlai@hku.hk-
dc.identifier.authorityLeung, JCK=rp00448en_US
dc.identifier.authorityTang, SCW=rp00480en_US
dc.identifier.authorityLai, KN=rp00324en_US
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1186/1479-5876-9-169en_US
dc.identifier.pmid21974877-
dc.identifier.pmcidPMC3203061-
dc.identifier.scopuseid_2-s2.0-80053480635en_US
dc.identifier.hkuros203978-
dc.identifier.volume9-
dc.identifier.issue1, article no. 169-
dc.identifier.isiWOS:000296706200001-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridLai, KN=7402135706en_US
dc.identifier.scopusauthoridLim, AI=52364409600en_US
dc.identifier.scopusauthoridChow, CW=52363242400en_US
dc.identifier.scopusauthoridLam, MF=7202630163en_US
dc.identifier.scopusauthoridTang, SCW=7403437082en_US
dc.identifier.scopusauthoridChan, LYY=35336076700en_US
dc.identifier.scopusauthoridLeung, JCK=7202180349en_US
dc.identifier.citeulike9861991-

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