Article: Differential effects of advanced glycation end-products on renal tubular cell inflammation

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TitleDifferential effects of advanced glycation end-products on renal tubular cell inflammation
AuthorsTang, SCW1
Chan, LYY1
Leung, JCK1
Cheng, AS1
Lin, M1
Lan, HY1
Lai, KN1
Keywordsadvanced glycation end-products
carboxymethyllysine albumin
chemokines
diabetic nephropathy
proximal tubular cells
Issue Date2011
PublisherBlackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journals/NEP
CitationNephrology, 2011, v. 16 n. 4, p. 417-425 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1440-1797.2010.01437.x
AbstractAim: The authors recently showed that advanced glycation end-products (AGE) in the form of glycated albumin (GA) upregulated renal tubular expression of interleukin (IL)-8 and soluble intercellular adhesion molecule-1 (sICAM-1), but not other important cytokines known to mediate diabetic nephropathy. This implies that other molecules such as the carbonyl intermediates of AGE or other modified protein lysine-albumin may participate in diabetic tubular injury. Methods: Human proximal tubular epithelial cells (PTEC) were growth-arrested and exposed to methylglyoxal (MG), MG-bovine serum albumin (BSA)-AGE, carboxymethyllysine (CML)-BSA, AGE-BSA or BSA with or without prior addition of rosiglitazone that was previously shown to attenuate the pro-inflammatory effect of GA alone. Results: MG-BSA-AGE and AGE-BSA upregulated tubular expression of connective tissue growth factor (CTGF), transforming growth factor (TGF)-β, and vascular endothelial growth factor (VEGF), whereas CML-BSA stimulated expression of IL-6, CCL-2, CTGF, TGF-β and VEGF. These AGE compounds also activated nuclear factor (NF)-ÎB and their effects were attenuated by pre-incubation with anti-RAGE antibody. MG and BSA did not affect the expression of any of these molecules. Rosiglitazone did not affect the in vitro biological effects of MG, MG-BSA-AGE, AGE-BSA or CML-BSA on PTEC. Conclusion: AGE exhibit differential inflammatory and fibrotic effects on PTEC via RAGE activation and NF-ÎB signal transduction. Rosiglitazone had no effect on these responses. Further investigations on compounds that nullify the downstream effects of these AGE are warranted. Tang and colleagues showed that various AGE formation (MG-BSA-AGE, AGE-BSA and CML-BSA are important AGE) have differential pro-inflammatory and profibrotic effects on cultured PTEC via RAGE activation and NF-ÎB signal transduction. © 2011 Asian Pacific Society of Nephrology.
ISSN1320-5358
2011 Impact Factor: 1.311
2011 SCImago Journal Rankings: 0.110
DOIhttp://dx.doi.org/10.1111/j.1440-1797.2010.01437.x
ISI Accession Number IDWOS:000289899500010
Funding AgencyGrant Number
Research Grants Council of Hong KongHKU 7764/07 M
Funding Information:

This work was supported by the Research Grants Council (General Research Fund number HKU 7764/07 M) of Hong Kong. Rosiglitazone was a kind gift from GlaxoSmithKline (Compound Management Division, Stevenage, Herts, UK).

ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorTang, SCW
dc.contributor.authorChan, LYY
dc.contributor.authorLeung, JCK
dc.contributor.authorCheng, AS
dc.contributor.authorLin, M
dc.contributor.authorLan, HY
dc.contributor.authorLai, KN
dc.date.accessioned2011-08-26T14:24:30Z
dc.date.available2011-08-26T14:24:30Z
dc.date.issued2011
dc.description.abstractAim: The authors recently showed that advanced glycation end-products (AGE) in the form of glycated albumin (GA) upregulated renal tubular expression of interleukin (IL)-8 and soluble intercellular adhesion molecule-1 (sICAM-1), but not other important cytokines known to mediate diabetic nephropathy. This implies that other molecules such as the carbonyl intermediates of AGE or other modified protein lysine-albumin may participate in diabetic tubular injury. Methods: Human proximal tubular epithelial cells (PTEC) were growth-arrested and exposed to methylglyoxal (MG), MG-bovine serum albumin (BSA)-AGE, carboxymethyllysine (CML)-BSA, AGE-BSA or BSA with or without prior addition of rosiglitazone that was previously shown to attenuate the pro-inflammatory effect of GA alone. Results: MG-BSA-AGE and AGE-BSA upregulated tubular expression of connective tissue growth factor (CTGF), transforming growth factor (TGF)-β, and vascular endothelial growth factor (VEGF), whereas CML-BSA stimulated expression of IL-6, CCL-2, CTGF, TGF-β and VEGF. These AGE compounds also activated nuclear factor (NF)-ÎB and their effects were attenuated by pre-incubation with anti-RAGE antibody. MG and BSA did not affect the expression of any of these molecules. Rosiglitazone did not affect the in vitro biological effects of MG, MG-BSA-AGE, AGE-BSA or CML-BSA on PTEC. Conclusion: AGE exhibit differential inflammatory and fibrotic effects on PTEC via RAGE activation and NF-ÎB signal transduction. Rosiglitazone had no effect on these responses. Further investigations on compounds that nullify the downstream effects of these AGE are warranted. Tang and colleagues showed that various AGE formation (MG-BSA-AGE, AGE-BSA and CML-BSA are important AGE) have differential pro-inflammatory and profibrotic effects on cultured PTEC via RAGE activation and NF-ÎB signal transduction. © 2011 Asian Pacific Society of Nephrology.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationNephrology, 2011, v. 16 n. 4, p. 417-425 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1440-1797.2010.01437.x
dc.identifier.citeulike8502227
dc.identifier.doihttp://dx.doi.org/10.1111/j.1440-1797.2010.01437.x
dc.identifier.epage425
dc.identifier.hkuros190809
dc.identifier.isiWOS:000289899500010
Funding AgencyGrant Number
Research Grants Council of Hong KongHKU 7764/07 M
Funding Information:

This work was supported by the Research Grants Council (General Research Fund number HKU 7764/07 M) of Hong Kong. Rosiglitazone was a kind gift from GlaxoSmithKline (Compound Management Division, Stevenage, Herts, UK).

dc.identifier.issn1320-5358
2011 Impact Factor: 1.311
2011 SCImago Journal Rankings: 0.110
dc.identifier.issue4
dc.identifier.pmid21143336
dc.identifier.scopuseid_2-s2.0-79955420320
dc.identifier.spage417
dc.identifier.urihttp://hdl.handle.net/10722/137407
dc.identifier.volume16
dc.languageeng
dc.publisherBlackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journals/NEP
dc.publisher.placeAustralia
dc.relation.ispartofNephrology
dc.relation.referencesReferences in Scopus
dc.rightsThe definitive version is available at www.blackwell-synergy.com
dc.subject.meshEpithelial Cells - drug effects - immunology - metabolism - pathology
dc.subject.meshGlycosylation End Products, Advanced - metabolism
dc.subject.meshInflammation Mediators - metabolism
dc.subject.meshKidney Tubules, Proximal - drug effects - immunology - metabolism - pathology
dc.subject.meshNephritis, Interstitial - immunology - metabolism - pathology - prevention and control
dc.subjectadvanced glycation end-products
dc.subjectcarboxymethyllysine albumin
dc.subjectchemokines
dc.subjectdiabetic nephropathy
dc.subjectproximal tubular cells
dc.titleDifferential effects of advanced glycation end-products on renal tubular cell inflammation
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong