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Article: Protective effect of peroxisome proliferator-activated receptor-gamma agonists on activated renal proximal tubular epithelial cells in IgA nephropathy

TitleProtective effect of peroxisome proliferator-activated receptor-gamma agonists on activated renal proximal tubular epithelial cells in IgA nephropathy
Authors
KeywordsAngiotensin II type 1 receptor
IgA nephropathy
PPAR-gamma agonist
Tubular epithelial cells
Tubulointerstitial injury
Issue Date2009
PublisherOxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/
Citation
Nephrology Dialysis Transplantation, 2009, v. 24 n. 7, p. 2067-2077 How to Cite?
AbstractBackground. We have previously demonstrated a glomerulo-tubular 'crosstalk' operating in the pathogenesis of tubulointerstitial injury in IgA nephropathy (IgAN). The present study aims to explore any possible beneficial effect of a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist in alleviating the tubulointerstitial inflammation in IgAN.Methods. Human proximal tubular epithelial cells (PTEC) were pre-treated with increasing concentration of a PPAR-γ agonist rosiglitazone or troglitazone (0-5 μM) followed by further incubation with the conditioned medium (IgA-HMC) collected from human mesangial cells (HMC) incubated with polymeric IgA isolated from IgAN patients. Gene expression of interleukin-6 (IL-6) and angiotensin II type 1 receptor (ATR1) was detected by reverse transcription-polymerase chain reaction (RT-PCR); protein expression of IL-6 and ATR1 was determined by ELISA and western blot, respectively. The mitogen-activated protein kinase extracellular signal-related kinase 12 (ERK12) activation was examined by western blot.Results. An IgA-HMC conditioned medium prepared from IgAN patients increased gene expression and protein synthesis of IL-6 and ATR1 in PTEC when compared with a conditioned medium prepared from healthy controls. The upregulated gene expression and protein synthesis of IL-6 and ATR1 in PTEC induced by the IgA-HMC conditioned medium were readily attenuated following pre-treatment with a PPAR-γ agonist, thiazolidinedione (TZD). The ATR1-downregulating effect exerted by the PPAR-γ agonist occurred through the inhibition of ERK12 activation. The PPAR-γ antagonist, GW9662, significantly attenuated the inhibitory action of rosiglitazone on the increased synthesis of IL-6 and ATR1 protein.Conclusion. Our current findings suggest that the PPAR-γ agonist attenuates excessive inflammatory response in activated PTEC in IgAN through suppressing ATR1 expression. This ATR1-downregulating effect is likely through the inhibition of ERK12 activation and is found to be PPAR-γ dependent. TZDs may possibly be new therapeutic additives to established treatment regime for renin-angiotensin system (RAS) blockade in IgAN.
Persistent Identifierhttp://hdl.handle.net/10722/59289
ISSN
2015 Impact Factor: 4.085
2015 SCImago Journal Rankings: 1.780
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorXiao, Jen_HK
dc.contributor.authorLeung, JCKen_HK
dc.contributor.authorChan, LYYen_HK
dc.contributor.authorGuo, Hen_HK
dc.contributor.authorLai, KNen_HK
dc.date.accessioned2010-05-31T03:47:04Z-
dc.date.available2010-05-31T03:47:04Z-
dc.date.issued2009en_HK
dc.identifier.citationNephrology Dialysis Transplantation, 2009, v. 24 n. 7, p. 2067-2077en_HK
dc.identifier.issn0931-0509en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59289-
dc.description.abstractBackground. We have previously demonstrated a glomerulo-tubular 'crosstalk' operating in the pathogenesis of tubulointerstitial injury in IgA nephropathy (IgAN). The present study aims to explore any possible beneficial effect of a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist in alleviating the tubulointerstitial inflammation in IgAN.Methods. Human proximal tubular epithelial cells (PTEC) were pre-treated with increasing concentration of a PPAR-γ agonist rosiglitazone or troglitazone (0-5 μM) followed by further incubation with the conditioned medium (IgA-HMC) collected from human mesangial cells (HMC) incubated with polymeric IgA isolated from IgAN patients. Gene expression of interleukin-6 (IL-6) and angiotensin II type 1 receptor (ATR1) was detected by reverse transcription-polymerase chain reaction (RT-PCR); protein expression of IL-6 and ATR1 was determined by ELISA and western blot, respectively. The mitogen-activated protein kinase extracellular signal-related kinase 12 (ERK12) activation was examined by western blot.Results. An IgA-HMC conditioned medium prepared from IgAN patients increased gene expression and protein synthesis of IL-6 and ATR1 in PTEC when compared with a conditioned medium prepared from healthy controls. The upregulated gene expression and protein synthesis of IL-6 and ATR1 in PTEC induced by the IgA-HMC conditioned medium were readily attenuated following pre-treatment with a PPAR-γ agonist, thiazolidinedione (TZD). The ATR1-downregulating effect exerted by the PPAR-γ agonist occurred through the inhibition of ERK12 activation. The PPAR-γ antagonist, GW9662, significantly attenuated the inhibitory action of rosiglitazone on the increased synthesis of IL-6 and ATR1 protein.Conclusion. Our current findings suggest that the PPAR-γ agonist attenuates excessive inflammatory response in activated PTEC in IgAN through suppressing ATR1 expression. This ATR1-downregulating effect is likely through the inhibition of ERK12 activation and is found to be PPAR-γ dependent. TZDs may possibly be new therapeutic additives to established treatment regime for renin-angiotensin system (RAS) blockade in IgAN.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/en_HK
dc.relation.ispartofNephrology Dialysis Transplantationen_HK
dc.subjectAngiotensin II type 1 receptoren_HK
dc.subjectIgA nephropathyen_HK
dc.subjectPPAR-gamma agonisten_HK
dc.subjectTubular epithelial cellsen_HK
dc.subjectTubulointerstitial injuryen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshChromans - therapeutic useen_HK
dc.subject.meshEpithelial Cells - drug effects - physiologyen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGlomerulonephritis, IGA - complicationsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshInflammation - etiology - prevention & controlen_HK
dc.subject.meshKidney Tubules, Proximal - cytologyen_HK
dc.subject.meshMaleen_HK
dc.subject.meshPPAR gamma - agonistsen_HK
dc.subject.meshThiazolidinediones - therapeutic useen_HK
dc.titleProtective effect of peroxisome proliferator-activated receptor-gamma agonists on activated renal proximal tubular epithelial cells in IgA nephropathyen_HK
dc.typeArticleen_HK
dc.identifier.emailLeung, JCK: jckleung@hku.hken_HK
dc.identifier.emailLai, KN: knlai@hku.hken_HK
dc.identifier.authorityLeung, JCK=rp00448en_HK
dc.identifier.authorityLai, KN=rp00324en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1093/ndt/gfn746en_HK
dc.identifier.pmid19155534-
dc.identifier.scopuseid_2-s2.0-67649979340en_HK
dc.identifier.hkuros161403en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67649979340&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume24en_HK
dc.identifier.issue7en_HK
dc.identifier.spage2067en_HK
dc.identifier.epage2077en_HK
dc.identifier.isiWOS:000267226500013-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridXiao, J=54887023900en_HK
dc.identifier.scopusauthoridLeung, JCK=7202180349en_HK
dc.identifier.scopusauthoridChan, LYY=55182644100en_HK
dc.identifier.scopusauthoridGuo, H=55468645700en_HK
dc.identifier.scopusauthoridLai, KN=7402135706en_HK

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