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      Possible Effects of Hepatocyte Growth Factor for the Prevention of Peritoneal Fibrosis


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          Objective: Some patients who had carried out long-term continuous ambulatory peritoneal dialysis discontinued the treatment because of progressive peritoneal fibrosis. It has been previously reported that transforming growth factor-β<sub>1</sub> (TGF-β<sub>1</sub>) is one of the factors that induces peritoneal fibrosis. Also, hepatocyte growth factor (HGF) plays a role in the prevention of fibrosis and in inhibiting TGF-β<sub>1</sub> production. In this study, we examined the effects of HGF on peritoneal fibrosis by TGF-β<sub>1</sub> induced by high concentrations of D-glucose. Design: We transfected a full-length human HGF cDNA in an expression vector into human peritoneal mesothelial cells (HPMCs) using the calcium phosphate method. Transfected HPMCs were cultured with high concentrations of D-glucose solution and co-cultured with fibroblasts using a transwell system. Cell proliferation was determined using the Tetra Color One method. TGF-β<sub>1</sub> and HGF protein were measured by enzyme-linked immunosorbent assay. Results: In addition to recombinant HGF, the growth inhibition of HPMCs by high concentration D-glucose or TGF-β<sub>1</sub> was significant. By transfecting HGF cDNA into HPMCs, growth inhibition by high concentration D-glucose was completely restored. Furthermore, the production of TGF-β<sub>1</sub> was also significantly decreased. Conclusion: These results suggested that exogenous HGF could possibly prevent peritoneal fibrosis.

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          Most cited references28

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          Hepatocyte growth factor gene therapy of liver cirrhosis in rats.

          Liver cirrhosis is the irreversible end result of fibrous scarring and hepatocellular regeneration, characterized by diffuse disorganization of the normal hepatic structure of regenerative nodules and fibrotic tissue. It is associated with prominent morbidity and mortality, and is induced by many factors, including chronic hepatitis virus infections, alcohol drinking and drug abuse. Hepatocyte growth factor (HGF), originally identified and cloned as a potent mitogen for hepatocytes, shows mitogenic, motogenic and morphogenic activities for a wide variety of cells. Moreover, HGF plays an essential part in the development and regeneration of the liver, and shows anti-apoptotic activity in hepatocytes. In a rat model of lethal liver cirrhosis produced by dimethylnitrosamine administrations, repeated transfections of the human HGF gene into skeletal muscles induced a high plasma level of human as well as enodogenous rat HGF, and tyrosine phosphorylation of the c-Met/HGF receptor. Transduction with the HGF gene also suppressed the increase of transforming growth factor-beta1 (TGF-beta1), which plays an essential part in the progression of liver cirrhosis, inhibited fibrogenesis and hepatocyte apoptosis, and produced the complete resolution of fibrosis in the cirrhotic liver, thereby improving the survival rate of rats with this severe illness. Thus, HGF gene therapy may be potentially useful for the treatment of patients with liver cirrhosis, which is otherwise fatal and untreatable by conventional therapy.
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            Isolation, culture and characterization of human peritoneal mesothelial cells.

            This study establishes a reproducible technique for the culture of human peritoneal mesothelial cells. Direct explants, as well as enzymatically degraded specimens, of human omentum have been used as the source of cells. Cells were grown on collagen and gelatin coated matrices and were maintained in supplemented Ham's F-12 medium containing 10% (vol/vol) Fetal calf serum. Morphologically and ultrastructurally, the cells formed a homogeneous population. They were polygonal when confluent and devoid of contaminating fibroblasts, endothelial cells and macrophages. Cultured mesothelial cells co-expressed cytokeratin and vimentin and synthesized laminin, fibronectin, mesosecrin, non-specific esterase and collagen Types I and III but not Type IV. Ultrastructural features included numerous surface microvilli, cytoplasmic vesicles and an abundant endoplasmic reticulum. The stimulation of mesothelial cells by the calcium ionophore A23187 demonstrated that the two major products of arachidonic acid metabolism were prostacyclin and prostaglandin E2. The peritoneal mesothelial cell may be pivotal in the initiation of the inflammatory response during peritonitis and its establishment in culture will provide the basis for an in vitro model of peritoneal inflammation.
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              Hepatocyte growth factor (HGF) as a tissue organizer for organogenesis and regeneration.


                Author and article information

                Nephron Exp Nephrol
                Cardiorenal Medicine
                S. Karger AG
                March 2005
                20 January 2005
                : 99
                : 3
                : e87-e94
                aDepartments of Hematology, Nephrology, and Rheumatology, Kinki University School of Medicine, and bDivision of Biochemistry, Department of Oncology, Biomedical Research Center, Osaka University Medical School, Osaka,Japan
                83416 Nephron Exp Nephrol 2005;99:e87–e94
                © 2005 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.

                : 07 January 2004
                : 09 August 2004
                Page count
                Figures: 7, References: 52, Pages: 1
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/83416
                Self URI (text/html): https://www.karger.com/Article/FullText/83416
                Self URI (journal page): https://www.karger.com/SubjectArea/Nephrology
                Original Paper

                Cardiovascular Medicine,Nephrology
                Hepatocyte growth factor,Peritoneal fibrosis,Continuous ambulatory peritoneal dialysis,TGF-β1 ,High concentration <italic>D</italic>-glucose,cDNA transfection,Co-culture, transwell system


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