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Article: Production and regulation of matrix metalloproteinases and their inhibitors by human peritoneal mesothelial cells

TitleProduction and regulation of matrix metalloproteinases and their inhibitors by human peritoneal mesothelial cells
Authors
Issue Date2000
PublisherMultimed, Inc. The Journal's web site is located at http://pdiconnect.com
Citation
Peritoneal Dialysis International, 2000, v. 20 n. 5, p. 524-533 How to Cite?
AbstractObjective: Human peritoneal mesothelial cells (HPMC) are likely to be involved in maintenance of the peritoneal membrane. We determined whether these cells were able to synthesize the matrix degrading enzymes, matrix metalloproteinases (MMPs), likely to be responsible for the breakdown of this membrane, and whether this secretion could be modulated by cytokines involved in the inflammatory response. Design: MMP activity in conditioned medium of growth-arrested HPMC was measured by zymography. Cultures were incubated in the presence and absence of the cytokines transforming growth factor-beta (TGFβ) and interleukin (IL)-1β in order to determine the effects of these cytokines on this process. The mRNA for these MMPs, together with that of their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs), was also examined by reverse transcriptase polymerase chain reaction (RT-PCR). Results: HPMC were shown to constitutively secrete the metalloproteinases MMP-2 and MMP-3 in vitro. In response to the proinflammatory cytokine IL-1β, the protein and mRNA for MMP-9 was induced, while secretion of MMP-2 was unaltered. Similarly, the mRNA for MMP-3 was also increased relative to actin following the addition of IL-1β. TGFβ was shown to slightly induce the secretion of MMP-2 together with the mRNA for TIMP I, TIMP II, and, to a greater extent, TIMP III. Used peritoneal dialysate was also shown to induce MMP-9 secretion, and this effect was blocked by the co-incubation of IL-1 receptor antagonist. The secretion of enzyme activity was shown to be from the apical surface of the cells. Conclusion: HPMC have the ability to control the accumulation of extracellular matrix by secreting the matrix degrading molecules MMP-2, MMP-3, and MMP-9. In addition, the secretion of these enzymes, together with that of their inhibitors (TIMPs) is regulated by the cytokines IL-1β and TGFβ. This process is likely to be important in both the normal maintenance of the integrity of the peritoneal membrane and in the changes that occur following prolonged peritoneal dialysis.
Persistent Identifierhttp://hdl.handle.net/10722/162369
ISSN
2015 Impact Factor: 1.298
2015 SCImago Journal Rankings: 0.683
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMartin, Jen_US
dc.contributor.authorYung, Sen_US
dc.contributor.authorRobson, RLen_US
dc.contributor.authorSteadman, Ren_US
dc.contributor.authorDavies, Men_US
dc.date.accessioned2012-09-05T05:19:19Z-
dc.date.available2012-09-05T05:19:19Z-
dc.date.issued2000en_US
dc.identifier.citationPeritoneal Dialysis International, 2000, v. 20 n. 5, p. 524-533en_US
dc.identifier.issn0896-8608en_US
dc.identifier.urihttp://hdl.handle.net/10722/162369-
dc.description.abstractObjective: Human peritoneal mesothelial cells (HPMC) are likely to be involved in maintenance of the peritoneal membrane. We determined whether these cells were able to synthesize the matrix degrading enzymes, matrix metalloproteinases (MMPs), likely to be responsible for the breakdown of this membrane, and whether this secretion could be modulated by cytokines involved in the inflammatory response. Design: MMP activity in conditioned medium of growth-arrested HPMC was measured by zymography. Cultures were incubated in the presence and absence of the cytokines transforming growth factor-beta (TGFβ) and interleukin (IL)-1β in order to determine the effects of these cytokines on this process. The mRNA for these MMPs, together with that of their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs), was also examined by reverse transcriptase polymerase chain reaction (RT-PCR). Results: HPMC were shown to constitutively secrete the metalloproteinases MMP-2 and MMP-3 in vitro. In response to the proinflammatory cytokine IL-1β, the protein and mRNA for MMP-9 was induced, while secretion of MMP-2 was unaltered. Similarly, the mRNA for MMP-3 was also increased relative to actin following the addition of IL-1β. TGFβ was shown to slightly induce the secretion of MMP-2 together with the mRNA for TIMP I, TIMP II, and, to a greater extent, TIMP III. Used peritoneal dialysate was also shown to induce MMP-9 secretion, and this effect was blocked by the co-incubation of IL-1 receptor antagonist. The secretion of enzyme activity was shown to be from the apical surface of the cells. Conclusion: HPMC have the ability to control the accumulation of extracellular matrix by secreting the matrix degrading molecules MMP-2, MMP-3, and MMP-9. In addition, the secretion of these enzymes, together with that of their inhibitors (TIMPs) is regulated by the cytokines IL-1β and TGFβ. This process is likely to be important in both the normal maintenance of the integrity of the peritoneal membrane and in the changes that occur following prolonged peritoneal dialysis.en_US
dc.languageengen_US
dc.publisherMultimed, Inc. The Journal's web site is located at http://pdiconnect.comen_US
dc.relation.ispartofPeritoneal Dialysis Internationalen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshEpithelium - Enzymologyen_US
dc.subject.meshHumansen_US
dc.subject.meshInterleukin-1 - Pharmacologyen_US
dc.subject.meshMatrix Metalloproteinase 2 - Metabolismen_US
dc.subject.meshMatrix Metalloproteinase 3 - Metabolismen_US
dc.subject.meshMatrix Metalloproteinases - Drug Effects - Metabolismen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshPeritoneum - Cytology - Enzymologyen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshSensitivity And Specificityen_US
dc.subject.meshTransforming Growth Factor Beta - Pharmacologyen_US
dc.titleProduction and regulation of matrix metalloproteinases and their inhibitors by human peritoneal mesothelial cellsen_US
dc.typeArticleen_US
dc.identifier.emailYung, S:ssyyung@hku.hken_US
dc.identifier.authorityYung, S=rp00455en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid11117243-
dc.identifier.scopuseid_2-s2.0-0033660521en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0033660521&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume20en_US
dc.identifier.issue5en_US
dc.identifier.spage524en_US
dc.identifier.epage533en_US
dc.identifier.isiWOS:000165418400007-
dc.publisher.placeCanadaen_US
dc.identifier.scopusauthoridMartin, J=7501553184en_US
dc.identifier.scopusauthoridYung, S=22636568800en_US
dc.identifier.scopusauthoridRobson, RL=7102721727en_US
dc.identifier.scopusauthoridSteadman, R=7005620093en_US
dc.identifier.scopusauthoridDavies, M=7404207291en_US

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