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      Metalloproteinase-9 mRNA Expression in Monocytes from Patients with Chronic Renal Failure

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          Abstract

          Long-term dialysis patients suffer from various complications including atherosclerosis. It has been suggested that metalloproteinases (MMPs) contribute to vascular remodeling during the development and progression of human atherosclerosis. Activated human monocytes have been demonstrated to secrete MMPs.In the present study, we measured levels of MMP mRNA in peripheral blood monocytes obtained from patients on continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD) and chronic-renal-failure patients not undergoing dialysis. Twenty patients with chronic renal failure were not undergoing dialysis, 20 patients were on CAPD, 40 patients were on chronic HD and 20 healthy volunteers served as controls. We used cDNA probes encoding for MMP-1, MMP-2, MMP-3 and MMP-9 and glyceraldehyde phosphate dehydrogenase. Higher levels of MMP-9 mRNA in the peripheral blood monocytes were observed in HD patients than in CAPD patients, undialyzed chronic renal failure patients or healthy controls. MMP-9 mRNA levels at the end of HD were not significantly higher than those at the start of HD. MMP-9 mRNA levels from HD patients did not differ among the types of membranes. We could detect minimal MMP-1, MMP-2 and MMP-3 mRNA expression in monocytes from all groups. Serum gelatinase activity was detectable in all samples; however, no significant differences existed among the groups.In summary, MMP-9 mRNA expression is enhanced in monocytes from HD and CAPD patients, and the enhancement may be, in part, associated with cardiovascular complications, including atherosclerosis, in dialysis patients. This increase in monocyte MMP-9 mRNA levels is lower in CAPD patients that it is in HD patients.

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          Most cited references 2

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          Metalloproteinases and their inhibitors in matrix remodeling.

          The matrix metalloproteinases are a tightly regulated family of enzymes that degrade extracellular matrix and basement membrane components. Recent evidence suggests that these proteases and their specific inhibitors play important roles in normal developmental processes and in pathological conditions. Interestingly, experiments designed to improve our understanding of metalloproteinase regulation have also resulted in new insights into mechanisms by which growth factors and proto-oncogenes may regulate biological processes.
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            Markedly elevated serum MMP-9 (gelatinase B) levels in rheumatoid arthritis: a potentially useful laboratory marker.

            In an attempt to find a potentially useful serum marker in rheumatoid arthritis (RA) which reflects underlying pathogenic mechanisms, we measured the circulating levels of matrix-degrading metalloproteinase-9 (MMP-9), also termed gelatinase B, in sera and synovial fluid (SF) from patients with RA and also quantitated the deposition and local synthesis of MMP-9 in RA synovium. Clinical samples, subjected to gelatin substrate zymography, antigenic immunoassay, and a quantitative substrate degradation assay, revealed elevated 92- and 72-kDa proenzyme forms of MMP-9 and MMP-2 in RA sera and SF compared with healthy controls. Immunostaining on fresh RA synovial specimens revealed MMP-9 within vascular walls in fibroblast-like cells and macrophages; mRNA synthesis was detected using reverse transcriptase in situ PCR. In summary, MMP-9 levels are substantially elevated in the sera and SF from patients with RA. The RA synovium is a source of this MMP-9 production, with abundant mRNA and protein observed within several different type of rheumatoid synovial cells.
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              Author and article information

              Journal
              AJN
              Am J Nephrol
              10.1159/issn.0250-8095
              American Journal of Nephrology
              S. Karger AG
              0250-8095
              1421-9670
              1998
              August 1998
              05 June 1998
              : 18
              : 4
              : 305-310
              Affiliations
              a Department of Medicine, Koto Hospital, and b Division of Nephrology, Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan
              Article
              13355 Am J Nephrol 1998;18:305–310
              10.1159/000013355
              9653834
              © 1998 S. Karger AG, Basel

              Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

              Page count
              Figures: 5, Tables: 1, References: 28, Pages: 6
              Product
              Self URI (application/pdf): https://www.karger.com/Article/Pdf/13355
              Categories
              Clinical Study

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