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Article: Activation of tubular epithelial cells in diabetic nephropathy and the role of the peroxisome proliferator-activated receptor-γ agonist

TitleActivation of tubular epithelial cells in diabetic nephropathy and the role of the peroxisome proliferator-activated receptor-γ agonist
Authors
Issue Date2006
PublisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org
Citation
Journal Of The American Society Of Nephrology, 2006, v. 17 n. 6, p. 1633-1643 How to Cite?
AbstractThe effects of advanced glycation end products (AGE) in the form of glycated albumin (GA) on the proinflammatory phenotype of cultured renal proximal tubular epithelial cells (PTEC) and the therapeutic potential of the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist were studied. Human PTEC were exposed to medium alone or supplemented with albumin or GA with or without previous addition of rosiglitazone (0.1 to 0.5 μM). Exposure to GA (up to 0.5 mg/ml) but not the equivalent dose of neat albumin significantly upregulated both mRNA and protein expression of IL-8 and soluble intercellular adhesion molecule-1 (sICAM-1) in a dose- and time-dependent manner. Using immunohistochemistry, ICAM-1 signals were detected in the tubular epithelia and peritubular capillaries in association with AGE deposition and leukocyte infiltration, whereas IL-8 staining was localized in the tubular epithelia of human diabetic kidney biopsies. Also in a dose-dependent manner, GA (0.5 mg/ml) but not albumin caused nuclear translocation of NF-κB and activation of mitogen-activated protein kinase (MAPK) p44/p42 and signal transducer and activator of transcription (STAT-1). Inhibition of these pathways with pyrrolidine dithiocarbamate, PD 98059, and fludarabine, respectively, attenuated GA-induced IL-8 secretion. Rosiglitazone dose-dependently attenuated GA-induced IL-8 and ICAM-1 signals in PTEC and completely abolished GA-induced STAT-1 signals but had no effect on NF-κB and MAPK activation. These findings suggest that AGE stimulate renal tubular expression of adhesion molecule and chemokine that together may account for the transmigration of inflammatory cells into the interstitial space during diabetic tubulopathy. Such proinflammatory phenotype may be partially modified by PPAR-γ ligation through STAT-1 inhibition independent of NF-κB transcriptional activity and MAPK signaling. Copyright © 2006 by the American Society of Nephrology.
Persistent Identifierhttp://hdl.handle.net/10722/162978
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTang, SCWen_US
dc.contributor.authorLeung, JCKen_US
dc.contributor.authorChan, LYYen_US
dc.contributor.authorTsang, AWLen_US
dc.contributor.authorLai, KNen_US
dc.date.accessioned2012-09-05T05:26:07Z-
dc.date.available2012-09-05T05:26:07Z-
dc.date.issued2006en_US
dc.identifier.citationJournal Of The American Society Of Nephrology, 2006, v. 17 n. 6, p. 1633-1643en_US
dc.identifier.issn1046-6673en_US
dc.identifier.urihttp://hdl.handle.net/10722/162978-
dc.description.abstractThe effects of advanced glycation end products (AGE) in the form of glycated albumin (GA) on the proinflammatory phenotype of cultured renal proximal tubular epithelial cells (PTEC) and the therapeutic potential of the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist were studied. Human PTEC were exposed to medium alone or supplemented with albumin or GA with or without previous addition of rosiglitazone (0.1 to 0.5 μM). Exposure to GA (up to 0.5 mg/ml) but not the equivalent dose of neat albumin significantly upregulated both mRNA and protein expression of IL-8 and soluble intercellular adhesion molecule-1 (sICAM-1) in a dose- and time-dependent manner. Using immunohistochemistry, ICAM-1 signals were detected in the tubular epithelia and peritubular capillaries in association with AGE deposition and leukocyte infiltration, whereas IL-8 staining was localized in the tubular epithelia of human diabetic kidney biopsies. Also in a dose-dependent manner, GA (0.5 mg/ml) but not albumin caused nuclear translocation of NF-κB and activation of mitogen-activated protein kinase (MAPK) p44/p42 and signal transducer and activator of transcription (STAT-1). Inhibition of these pathways with pyrrolidine dithiocarbamate, PD 98059, and fludarabine, respectively, attenuated GA-induced IL-8 secretion. Rosiglitazone dose-dependently attenuated GA-induced IL-8 and ICAM-1 signals in PTEC and completely abolished GA-induced STAT-1 signals but had no effect on NF-κB and MAPK activation. These findings suggest that AGE stimulate renal tubular expression of adhesion molecule and chemokine that together may account for the transmigration of inflammatory cells into the interstitial space during diabetic tubulopathy. Such proinflammatory phenotype may be partially modified by PPAR-γ ligation through STAT-1 inhibition independent of NF-κB transcriptional activity and MAPK signaling. Copyright © 2006 by the American Society of Nephrology.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.meshCell Lineen_US
dc.subject.meshDiabetic Nephropathies - Metabolism - Pathologyen_US
dc.subject.meshEnzyme Inhibitors - Pharmacologyen_US
dc.subject.meshEpithelial Cells - Cytologyen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunohistochemistryen_US
dc.subject.meshInterleukin-8 - Metabolismen_US
dc.subject.meshKidney - Cytologyen_US
dc.subject.meshMap Kinase Signaling Systemen_US
dc.subject.meshNf-Kappa B - Metabolismen_US
dc.subject.meshPpar Gamma - Agonistsen_US
dc.subject.meshRna, Messenger - Metabolismen_US
dc.subject.meshStat1 Transcription Factor - Metabolismen_US
dc.subject.meshSignal Transductionen_US
dc.subject.meshThiazolidinediones - Pharmacologyen_US
dc.titleActivation of tubular epithelial cells in diabetic nephropathy and the role of the peroxisome proliferator-activated receptor-γ agonisten_US
dc.typeArticleen_US
dc.identifier.emailTang, SCW:scwtang@hku.hken_US
dc.identifier.emailLeung, JCK:jckleung@hku.hken_US
dc.identifier.emailLai, KN:knlai@hku.hken_US
dc.identifier.authorityTang, SCW=rp00480en_US
dc.identifier.authorityLeung, JCK=rp00448en_US
dc.identifier.authorityLai, KN=rp00324en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1681/ASN.2005101113en_US
dc.identifier.pmid16687627-
dc.identifier.scopuseid_2-s2.0-33646945290en_US
dc.identifier.hkuros121480-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33646945290&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume17en_US
dc.identifier.issue6en_US
dc.identifier.spage1633en_US
dc.identifier.epage1643en_US
dc.identifier.eissn1533-3450-
dc.identifier.isiWOS:000237891100015-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridTang, SCW=7403437082en_US
dc.identifier.scopusauthoridLeung, JCK=7202180349en_US
dc.identifier.scopusauthoridChan, LYY=8108378300en_US
dc.identifier.scopusauthoridTsang, AWL=7006979244en_US
dc.identifier.scopusauthoridLai, KN=7402135706en_US
dc.identifier.citeulike1674773-

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