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Article: Regulation of CCN2/CTGF and related cytokines in cultured peritoneal cells under conditions simulating peritoneal dialysis

TitleRegulation of CCN2/CTGF and related cytokines in cultured peritoneal cells under conditions simulating peritoneal dialysis
Authors
KeywordsCAPD
CTGF/CCN2
Mesothelial cell
TGF-β
VEGF
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. 2, p. 458-469 How to Cite?
AbstractBackground. Continuous ambulatory peritoneal dialysis (CAPD) is a major treatment modality for end-stage renal failure. The peritoneal membrane exhibits pathological changes that correlate with the duration of dialysis. These changes are due to the exposure of the peritoneum to non-physiologic peritoneal dialysis solution (PDS) with a high glucose content, and containing potentially toxic substances including glucose degradation products (GDP) and advanced glycation end products (AGE). Connective tissue growth factor (CTGF/CCN2) is one of the determinants of progressive fibrosis and peritoneal membrane dysfunction in CAPD. In this study, we examined the CCN2 expression and its regulation in peritoneal resident cells using a cell culture model. Methods. The expression of transforming growth factor-β (TGF-β), CCN2 and vascular endothelial growth factor (VEGF) in human peritoneal mesothelial cells (HPMC), human peritoneal fibroblasts (HPF) or endothelial cell line EA.hy926 (EC) cultured with various PDS and their components was examined by quantitative PCR (qPCR). The modulation of CCN2 synthesis under the crosstalk between HPMC and HPF or EC was examined using a conditioned medium transfer system in which HPMC was exposed to conditioned media obtained from HPF or EC incubated with PDS and their components. The differential effects of TGF-β, CCN2 and VEGF in inducing the expression of transcriptional factors as well as interleukin-6 (IL-6), matrix metallopeptidase 9 (MMP-9) and collagen I were examined by electrophoretic mobility-shift assay (EMSA) and qPCR. Results. PDS and their components differentially modulated the expression of TGF-β, CCN2 and VEGF in HPMC, HPF and EC. The expression of CCN2 by HPMC was significantly increased after cultured with a HPF-conditioned medium and an EC-conditioned medium. Neutralizing anti-TGF-β antibodies reduced but not completely abolished the CCN2 synthesis in HPMC cultured with the HPF- or EC-conditioned medium. CCN2, TGF-β and VEGF activated distinct transcriptional factors in HPMC, which resulted in divergent biological responses in terms of IL-6, MMP-9 and collagen I mRNA expression. Conclusion. AGE and GDPs in PDS differentially regulate the synthesis of CCN2 by peritoneal resident cells. The CCN2 synthesis by HPMC can be further amplified by TGF-β released from HPF or EC. The differential activation of different transcriptional factors and diverse response of HPMC towards CCN2, TGF-β and VEGF suggest that these cytokines/growth factors have an overlapping and distinct role on HPMC. © The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/59269
ISSN
2015 Impact Factor: 4.085
2015 SCImago Journal Rankings: 1.780
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council, Hong KongHKU 7415/04M
L & T Charitable Fund
House of INDOCAFE
Funding Information:

The study was partly supported by the Research Grant Council, Hong Kong (HKU 7415/04M). JCL was supported by the L & T Charitable Fund and the House of INDOCAFE.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorLeung, JCKen_HK
dc.contributor.authorChan, LYYen_HK
dc.contributor.authorTam, KYen_HK
dc.contributor.authorTang, SCWen_HK
dc.contributor.authorLam, MFen_HK
dc.contributor.authorCheng, ASen_HK
dc.contributor.authorChu, KMen_HK
dc.contributor.authorLai, KNen_HK
dc.date.accessioned2010-05-31T03:46:36Z-
dc.date.available2010-05-31T03:46:36Z-
dc.date.issued2009en_HK
dc.identifier.citationNephrology Dialysis Transplantation, 2009, v. 24 n. 2, p. 458-469en_HK
dc.identifier.issn0931-0509en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59269-
dc.description.abstractBackground. Continuous ambulatory peritoneal dialysis (CAPD) is a major treatment modality for end-stage renal failure. The peritoneal membrane exhibits pathological changes that correlate with the duration of dialysis. These changes are due to the exposure of the peritoneum to non-physiologic peritoneal dialysis solution (PDS) with a high glucose content, and containing potentially toxic substances including glucose degradation products (GDP) and advanced glycation end products (AGE). Connective tissue growth factor (CTGF/CCN2) is one of the determinants of progressive fibrosis and peritoneal membrane dysfunction in CAPD. In this study, we examined the CCN2 expression and its regulation in peritoneal resident cells using a cell culture model. Methods. The expression of transforming growth factor-β (TGF-β), CCN2 and vascular endothelial growth factor (VEGF) in human peritoneal mesothelial cells (HPMC), human peritoneal fibroblasts (HPF) or endothelial cell line EA.hy926 (EC) cultured with various PDS and their components was examined by quantitative PCR (qPCR). The modulation of CCN2 synthesis under the crosstalk between HPMC and HPF or EC was examined using a conditioned medium transfer system in which HPMC was exposed to conditioned media obtained from HPF or EC incubated with PDS and their components. The differential effects of TGF-β, CCN2 and VEGF in inducing the expression of transcriptional factors as well as interleukin-6 (IL-6), matrix metallopeptidase 9 (MMP-9) and collagen I were examined by electrophoretic mobility-shift assay (EMSA) and qPCR. Results. PDS and their components differentially modulated the expression of TGF-β, CCN2 and VEGF in HPMC, HPF and EC. The expression of CCN2 by HPMC was significantly increased after cultured with a HPF-conditioned medium and an EC-conditioned medium. Neutralizing anti-TGF-β antibodies reduced but not completely abolished the CCN2 synthesis in HPMC cultured with the HPF- or EC-conditioned medium. CCN2, TGF-β and VEGF activated distinct transcriptional factors in HPMC, which resulted in divergent biological responses in terms of IL-6, MMP-9 and collagen I mRNA expression. Conclusion. AGE and GDPs in PDS differentially regulate the synthesis of CCN2 by peritoneal resident cells. The CCN2 synthesis by HPMC can be further amplified by TGF-β released from HPF or EC. The differential activation of different transcriptional factors and diverse response of HPMC towards CCN2, TGF-β and VEGF suggest that these cytokines/growth factors have an overlapping and distinct role on HPMC. © The Author [2008]. 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.subjectCAPDen_HK
dc.subjectCTGF/CCN2en_HK
dc.subjectMesothelial cellen_HK
dc.subjectTGF-βen_HK
dc.subjectVEGFen_HK
dc.subject.meshCell Proliferation - drug effectsen_HK
dc.subject.meshCell Survival - drug effectsen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshCollagen Type I - geneticsen_HK
dc.subject.meshConnective Tissue Growth Factor - genetics - metabolismen_HK
dc.subject.meshCulture Media, Conditioneden_HK
dc.subject.meshCytokines - genetics - metabolismen_HK
dc.subject.meshDialysis Solutions - toxicityen_HK
dc.subject.meshEndothelial Cells - drug effects - metabolism - pathologyen_HK
dc.subject.meshEpithelial Cells - drug effects - metabolism - pathologyen_HK
dc.subject.meshFibroblasts - drug effects - metabolism - pathologyen_HK
dc.subject.meshGene Expression - drug effectsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshInterleukin-6 - geneticsen_HK
dc.subject.meshMatrix Metalloproteinase 9 - geneticsen_HK
dc.subject.meshPeritoneal Dialysis, Continuous Ambulatory - adverse effectsen_HK
dc.subject.meshPeritoneum - drug effects - metabolism - pathologyen_HK
dc.subject.meshPolymerase Chain Reactionen_HK
dc.subject.meshRNA, Messenger - genetics - metabolismen_HK
dc.subject.meshTransforming Growth Factor beta - genetics - metabolismen_HK
dc.subject.meshVascular Endothelial Growth Factor A - genetics - metabolismen_HK
dc.titleRegulation of CCN2/CTGF and related cytokines in cultured peritoneal cells under conditions simulating peritoneal dialysisen_HK
dc.typeArticleen_HK
dc.identifier.emailLeung, JCK: jckleung@hku.hken_HK
dc.identifier.emailTang, SCW: scwtang@hku.hken_HK
dc.identifier.emailChu, KM: chukm@hkucc.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.authorityChu, KM=rp00435en_HK
dc.identifier.authorityLai, KN=rp00324en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/ndt/gfn524en_HK
dc.identifier.pmid18805993-
dc.identifier.scopuseid_2-s2.0-58449116650en_HK
dc.identifier.hkuros154620en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-58449116650&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume24en_HK
dc.identifier.issue2en_HK
dc.identifier.spage458en_HK
dc.identifier.epage469en_HK
dc.identifier.isiWOS:000262525900023-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectPeritoneal membrane dysfunction in continuous ambulatory peritoneal dialysis (CAPD): the role of connective tissue growth factor (CTGF)-
dc.identifier.scopusauthoridLeung, JCK=7202180349en_HK
dc.identifier.scopusauthoridChan, LYY=55182644100en_HK
dc.identifier.scopusauthoridTam, KY=25930206700en_HK
dc.identifier.scopusauthoridTang, SCW=7403437082en_HK
dc.identifier.scopusauthoridLam, MF=35300050600en_HK
dc.identifier.scopusauthoridCheng, AS=21733421700en_HK
dc.identifier.scopusauthoridChu, KM=7402453538en_HK
dc.identifier.scopusauthoridLai, KN=7402135706en_HK
dc.identifier.citeulike4211824-

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