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Article: Reduction of Perlecan Synthesis and Induction of TGF-β1 in Human Peritoneal Mesothelial Cells Due to High Dialysate Glucose Concentration: Implication in Peritoneal Dialysis

TitleReduction of Perlecan Synthesis and Induction of TGF-β1 in Human Peritoneal Mesothelial Cells Due to High Dialysate Glucose Concentration: Implication in Peritoneal Dialysis
Authors
Issue Date2004
PublisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org
Citation
Journal Of The American Society Of Nephrology, 2004, v. 15 n. 5, p. 1178-1188 How to Cite?
AbstractProlonged exposure of the peritoneal mesothelium to high dialysate glucose concentrations reduces anionic sites that are critical to its selective permeability, thereby impairing the peritoneal transport properties in patients on long-term peritoneal dialysis (PD). Perlecan, an anionic heparan sulfate proteoglycan, is pivotal to the selective permeability of basement membranes, and high glucose concentrations modulate its synthesis in mesangial cells. The effect of glucose on perlecan expression in the peritoneal mesothelium has not been established. We investigated perlecan expression in peritoneal biopsies from patients on PD, and the effect of high glucose concentrations on perlecan synthesis in cultured human peritoneal mesothelial cells (HPMC). Peritoneal biopsies from PD patients showed reduced perlecan expression compared with controls. Exposure of HPMC to high glucose concentrations resulted in a dose-dependent reduction in the synthesis of perlecan polypeptide and its deposition into the extracellular matrix. These effects were mediated in part through the induction of TGF-β1. Characterization studies showed that perlecan synthesized by HPMC contained solely heparan sulfate glycosaminoglycan (HS GAG) chains, and [35S]-incorporation studies demonstrated progressive reduction of their de novo synthesis with increasing glucose concentrations (68142 ± 3658, 48147 ± 2517, 31468 ± 5781, and 25575 ± 3621 cpm/μg cellular protein for 5 mM, 30 mM, 75 mM, and 120 mM D-glucose, respectively; P < 0.001 for 5 mM versus 30 mM D-glucose, and P < 0.0001 for 5 mM versus 75 mM or 120 mM D-glucose). Both the length and the charge density of the HS GAG chains remained unchanged. Reduction of peritoneal perlecan expression in long-term PD was attributed to high dialysate glucose concentrations, which induced TGF-β1 and reduced perlecan synthesis in HPMC. Since perlecan can sequester growth factors, thereby modulating cell migration and differentiation perturbation of peritoneal perlecan expression contributes to the structural and functional changes of the peritoneum in long-term PD.
Persistent Identifierhttp://hdl.handle.net/10722/162846
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYung, Sen_US
dc.contributor.authorChen, XRen_US
dc.contributor.authorTsang, RCWen_US
dc.contributor.authorZhang, Qen_US
dc.contributor.authorChan, TMen_US
dc.date.accessioned2012-09-05T05:24:18Z-
dc.date.available2012-09-05T05:24:18Z-
dc.date.issued2004en_US
dc.identifier.citationJournal Of The American Society Of Nephrology, 2004, v. 15 n. 5, p. 1178-1188en_US
dc.identifier.issn1046-6673en_US
dc.identifier.urihttp://hdl.handle.net/10722/162846-
dc.description.abstractProlonged exposure of the peritoneal mesothelium to high dialysate glucose concentrations reduces anionic sites that are critical to its selective permeability, thereby impairing the peritoneal transport properties in patients on long-term peritoneal dialysis (PD). Perlecan, an anionic heparan sulfate proteoglycan, is pivotal to the selective permeability of basement membranes, and high glucose concentrations modulate its synthesis in mesangial cells. The effect of glucose on perlecan expression in the peritoneal mesothelium has not been established. We investigated perlecan expression in peritoneal biopsies from patients on PD, and the effect of high glucose concentrations on perlecan synthesis in cultured human peritoneal mesothelial cells (HPMC). Peritoneal biopsies from PD patients showed reduced perlecan expression compared with controls. Exposure of HPMC to high glucose concentrations resulted in a dose-dependent reduction in the synthesis of perlecan polypeptide and its deposition into the extracellular matrix. These effects were mediated in part through the induction of TGF-β1. Characterization studies showed that perlecan synthesized by HPMC contained solely heparan sulfate glycosaminoglycan (HS GAG) chains, and [35S]-incorporation studies demonstrated progressive reduction of their de novo synthesis with increasing glucose concentrations (68142 ± 3658, 48147 ± 2517, 31468 ± 5781, and 25575 ± 3621 cpm/μg cellular protein for 5 mM, 30 mM, 75 mM, and 120 mM D-glucose, respectively; P < 0.001 for 5 mM versus 30 mM D-glucose, and P < 0.0001 for 5 mM versus 75 mM or 120 mM D-glucose). Both the length and the charge density of the HS GAG chains remained unchanged. Reduction of peritoneal perlecan expression in long-term PD was attributed to high dialysate glucose concentrations, which induced TGF-β1 and reduced perlecan synthesis in HPMC. Since perlecan can sequester growth factors, thereby modulating cell migration and differentiation perturbation of peritoneal perlecan expression contributes to the structural and functional changes of the peritoneum in long-term PD.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.rightsAmerican Journal of Nephrology. Copyright © S Karger AG.-
dc.subject.meshBiopsyen_US
dc.subject.meshCell Division - Drug Effectsen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshDialysis Solutions - Pharmacologyen_US
dc.subject.meshEpitheliumen_US
dc.subject.meshGlucose - Pharmacologyen_US
dc.subject.meshHeparan Sulfate Proteoglycans - Biosynthesisen_US
dc.subject.meshHumansen_US
dc.subject.meshPeritoneal Dialysisen_US
dc.subject.meshPeritoneum - Cytology - Drug Effects - Metabolismen_US
dc.subject.meshSulfur Radioisotopes - Diagnostic Useen_US
dc.subject.meshTransforming Growth Factor Beta - Metabolism - Secretionen_US
dc.subject.meshTransforming Growth Factor Beta1en_US
dc.titleReduction of Perlecan Synthesis and Induction of TGF-β1 in Human Peritoneal Mesothelial Cells Due to High Dialysate Glucose Concentration: Implication in Peritoneal Dialysisen_US
dc.typeArticleen_US
dc.identifier.emailYung, S:ssyyung@hku.hken_US
dc.identifier.emailChan, TM:dtmchan@hku.hken_US
dc.identifier.authorityYung, S=rp00455en_US
dc.identifier.authorityChan, TM=rp00394en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1097/01.ASN.0000122826.40921.D7en_US
dc.identifier.pmid15100358-
dc.identifier.scopuseid_2-s2.0-1942506715en_US
dc.identifier.hkuros132104-
dc.identifier.hkuros88132-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-1942506715&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume15en_US
dc.identifier.issue5en_US
dc.identifier.spage1178en_US
dc.identifier.epage1188en_US
dc.identifier.isiWOS:000221043000012-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridYung, S=22636568800en_US
dc.identifier.scopusauthoridChen, XR=15031500100en_US
dc.identifier.scopusauthoridTsang, RCW=36808555100en_US
dc.identifier.scopusauthoridZhang, Q=7406720527en_US
dc.identifier.scopusauthoridChan, TM=7402687700en_US

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