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Article: Glucose degradation products downregulate ZO-1 expression in human peritoneal mesothelial cells: The role of VEGF

TitleGlucose degradation products downregulate ZO-1 expression in human peritoneal mesothelial cells: The role of VEGF
Authors
KeywordsGlucose degradation products
Peritoneal dialysis
Peritoneal mesothelial cells
Vascular endothelial growth factor
Zonula occludens protein 1
Issue Date2005
PublisherOxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/
Citation
Nephrology Dialysis Transplantation, 2005, v. 20 n. 7, p. 1336-1349 How to Cite?
AbstractBackground. Glucose degradation products (GDPs) are formed during heat sterilization of peritoneal dialysis fluid and, to a lesser extent, during their prolonged storage. In vitro studies have demonstrated that GDPs impair functions of peritoneal mesothelial cells, including proliferation, viability and cytokine release. In the present study, we studied the acute effect of GDPs on the expression of tight junction-associated protein, zonula occludens protein 1 (ZO-1), in human peritoneal mesothelial cells (HPMC). The role of the vascular endothelial growth factor (VEGF) induced by GDPs in the expression of ZO-1 was also examined. Methods. HPMC were cultured with GDPs, including 2-furaldehyde (FurA), methylglyoxal (M-Glx) and 3,4-dideoxyglucosone-3-ene (3,4-DGE). The expression of ZO-1 and the synthesis of VEGF were examined. To define the role of VEGF on the regulation of ZO-1 expression, HPMC were cultured with GDPs in the presence or absence of neutralizing antibody to VEGF. The signal pathways involved in VEGF synthesis induced by GDPs were also characterized. Results. ZO-1 expression in HPMC was downregulated in a time- and dose-dependent manner following culture with subtoxic concentrations of GDPs (FurA, M-Glx and 3,4-DGE). All three GDPs increased VEGF synthesis in HPMC. Exogenous VEGF downregulated the expression of ZO-1 and neutralizing anti-VEGF antibody reversed the effect of GDPs on ZO-1 expression in HPMC, suggesting the action of GDPs on ZO-1 expression was mediated by VEGF. All three GDPs activated the p42/p44 mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) signal transduction pathways. The GDP-induced VEGF and transforming growth factor (TGF)-β synthesis in HPMC was partially reduced by either the p42/ p44 MAPK inhibitor (PD98059) or the PKC inhibitor (staurosporine). More importantly, the VEGF and TGF-β synthesis induced by GDPs in HPMC was completely blocked by synergistic action of both inhibitors. Conclusions. We have demonstrated that short-term exposure to GDPs downregulates ZO-1 expression in HPMC through the generation of VEGF. Our study provides evidence that GDPs can directly induce VEGF and TGF-β production in HPMC through the activation of p42/p44 MAPK and PKC signal transduction pathways. © The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/77308
ISSN
2015 Impact Factor: 4.085
2015 SCImago Journal Rankings: 1.780
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLeung, JCKen_HK
dc.contributor.authorChan, LYen_HK
dc.contributor.authorLi, FFKen_HK
dc.contributor.authorTang, SCWen_HK
dc.contributor.authorChan, KWen_HK
dc.contributor.authorChan, TMen_HK
dc.contributor.authorLam, MFen_HK
dc.contributor.authorWieslander, Aen_HK
dc.contributor.authorLai, KNen_HK
dc.date.accessioned2010-09-06T07:30:30Z-
dc.date.available2010-09-06T07:30:30Z-
dc.date.issued2005en_HK
dc.identifier.citationNephrology Dialysis Transplantation, 2005, v. 20 n. 7, p. 1336-1349en_HK
dc.identifier.issn0931-0509en_HK
dc.identifier.urihttp://hdl.handle.net/10722/77308-
dc.description.abstractBackground. Glucose degradation products (GDPs) are formed during heat sterilization of peritoneal dialysis fluid and, to a lesser extent, during their prolonged storage. In vitro studies have demonstrated that GDPs impair functions of peritoneal mesothelial cells, including proliferation, viability and cytokine release. In the present study, we studied the acute effect of GDPs on the expression of tight junction-associated protein, zonula occludens protein 1 (ZO-1), in human peritoneal mesothelial cells (HPMC). The role of the vascular endothelial growth factor (VEGF) induced by GDPs in the expression of ZO-1 was also examined. Methods. HPMC were cultured with GDPs, including 2-furaldehyde (FurA), methylglyoxal (M-Glx) and 3,4-dideoxyglucosone-3-ene (3,4-DGE). The expression of ZO-1 and the synthesis of VEGF were examined. To define the role of VEGF on the regulation of ZO-1 expression, HPMC were cultured with GDPs in the presence or absence of neutralizing antibody to VEGF. The signal pathways involved in VEGF synthesis induced by GDPs were also characterized. Results. ZO-1 expression in HPMC was downregulated in a time- and dose-dependent manner following culture with subtoxic concentrations of GDPs (FurA, M-Glx and 3,4-DGE). All three GDPs increased VEGF synthesis in HPMC. Exogenous VEGF downregulated the expression of ZO-1 and neutralizing anti-VEGF antibody reversed the effect of GDPs on ZO-1 expression in HPMC, suggesting the action of GDPs on ZO-1 expression was mediated by VEGF. All three GDPs activated the p42/p44 mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) signal transduction pathways. The GDP-induced VEGF and transforming growth factor (TGF)-β synthesis in HPMC was partially reduced by either the p42/ p44 MAPK inhibitor (PD98059) or the PKC inhibitor (staurosporine). More importantly, the VEGF and TGF-β synthesis induced by GDPs in HPMC was completely blocked by synergistic action of both inhibitors. Conclusions. We have demonstrated that short-term exposure to GDPs downregulates ZO-1 expression in HPMC through the generation of VEGF. Our study provides evidence that GDPs can directly induce VEGF and TGF-β production in HPMC through the activation of p42/p44 MAPK and PKC signal transduction pathways. © The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.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.rightsNephrology, Dialysis, Transplantation. Copyright © Oxford University Press.en_HK
dc.subjectGlucose degradation productsen_HK
dc.subjectPeritoneal dialysisen_HK
dc.subjectPeritoneal mesothelial cellsen_HK
dc.subjectVascular endothelial growth factoren_HK
dc.subjectZonula occludens protein 1en_HK
dc.titleGlucose degradation products downregulate ZO-1 expression in human peritoneal mesothelial cells: The role of VEGFen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0931-0509&volume=20&issue=7&spage=1336&epage=1349&date=2005&atitle=Glucose+degradation+products+downregulate+ZO-1+expression+in+human+peritoneal+mesothelial+cells:+the+role+of+VEGFen_HK
dc.identifier.emailLeung, JCK: jckleung@hku.hken_HK
dc.identifier.emailTang, SCW: scwtang@hku.hken_HK
dc.identifier.emailChan, KW: hrmtckw@hku.hken_HK
dc.identifier.emailChan, TM: dtmchan@hku.hken_HK
dc.identifier.emailLai, KN: knlai@hku.hken_HK
dc.identifier.authorityLeung, JCK=rp00448en_HK
dc.identifier.authorityTang, SCW=rp00480en_HK
dc.identifier.authorityChan, KW=rp00330en_HK
dc.identifier.authorityChan, TM=rp00394en_HK
dc.identifier.authorityLai, KN=rp00324en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/ndt/gfh814en_HK
dc.identifier.scopuseid_2-s2.0-26044434659en_HK
dc.identifier.hkuros121574en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-26044434659&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume20en_HK
dc.identifier.issue7en_HK
dc.identifier.spage1336en_HK
dc.identifier.epage1349en_HK
dc.identifier.isiWOS:000230858800011-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLeung, JCK=7202180349en_HK
dc.identifier.scopusauthoridChan, LY=8108378300en_HK
dc.identifier.scopusauthoridLi, FFK=55210612400en_HK
dc.identifier.scopusauthoridTang, SCW=7403437082en_HK
dc.identifier.scopusauthoridChan, KW=16444133100en_HK
dc.identifier.scopusauthoridChan, TM=7402687700en_HK
dc.identifier.scopusauthoridLam, MF=7202630163en_HK
dc.identifier.scopusauthoridWieslander, A=7005892114en_HK
dc.identifier.scopusauthoridLai, KN=7402135706en_HK
dc.identifier.citeulike236980-

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