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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

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      About Blood Purification: 3.0 Impact Factor I 5.6 CiteScore I 0.83 Scimago Journal & Country Rank (SJR)

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      Tamoxifen Downregulates Connective Tissue Growth Factor to Ameliorate Peritoneal Fibrosis

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          Abstract

          Peritoneal fibrosis (PF), including simple sclerosis and encapsulating peritoneal sclerosis (EPS), is a serious complication in patients on long-term peritoneal dialysis. Tamoxifen has successfully been used in treating EPS; however, the mechanism of tamoxifen in treating EPS fibrosis disorders remains unclear. This study demonstrates a possible antifibrotic mechanism of tamoxifen. A bleach-induced PF rat model was applied as the in vivo treatment target. Tamoxifen was intraperitoneally injected daily to treat PF. The PF scores and thickness of the submesothelial zone over the liver surface were measured as indicators for the severity of PF. Human peritoneal mesothelial cells (HPMC) were used as an in vitro model to test the antifibrotic effect of tamoxifen. Gene expressions of transforming growth factors-β (TGF-β), connective tissue growth factor (CTGF) and collagen were investigated using quantitative polymerase chain reactions. In HPMC, tamoxifen showed paradoxical effects between collagen I and TGF-β. Tamoxifen also inhibited TGF-β-induced collagen and CTGF. The possible antifibrotic effect of tamoxifen is through inhibiting CTGF to block collagen synthesis, although it enhances TGF-β which increases fibrosis. These results provide a possible molecular mechanism for tamoxifen.

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          Transient overexpression of TGF-{beta}1 induces epithelial mesenchymal transition in the rodent peritoneum.

          Philippe Bonniaud, Peter Margetts, Edward C Holmes … (2005)
          Epithelial mesenchymal transition (EMT), a process involved in many growth and repair functions, has been identified in the peritoneal tissues of patients who undergo peritoneal dialysis. The sequence of changes in gene regulation and cellular events associated with EMT after TGF-beta1-induced peritoneal fibrosis is reported. Sprague-Dawley rats received an intraperitoneal injection of an adenovirus vector that transfers active TGF-beta1 (AdTGF-beta1) or control adenovirus, AdDL. Animals were killed 0 to 21 days after infection. Peritoneal effluent and tissue were analyzed for markers of EMT. In the animals that were treated with AdTGF-beta1, an increase in expression of genes associated with EMT and fibrosis, such as type I collagen A2, alpha-smooth muscle actin, and the zinc finger regulatory protein Snail, was identified. Transition of mesothelial cells 4 to 7 d after infection, with appearance of epithelial cells in the submesothelial zone 7 to 14 d after exposure to AdTGF-beta1, was demonstrated. This phase was associated with disruption of the basement membrane and increased expression of matrix metalloproteinase 2. By 14 to 21 d after infection, there was evidence of restoration of normal submesothelial architecture. These findings suggest that EMT occurs in vivo after TGF-beta1 overexpression in the peritoneum. Cellular changes and gene regulation associated with EMT are evident throughout the fibrogenic process and are not limited to early time points. This further supports the central role of TGF-beta1 in peritoneal fibrosis and provides an important model to study the sequence of events involved in TGF-beta1-induced EMT.
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            Sclerosing mesenteritis: clinical features, treatment, and outcome in ninety-two patients.

            D Akram, Darrell Pardi, Carlos A Schaffner … (2007)
            Sclerosing mesenteritis is a rare non-neoplastic disease that affects the small bowel mesentery with chronic fibrosing inflammation. There are few data on the natural history and therapeutic options for this condition. We performed a retrospective and prospective study to describe the clinical characteristics, therapy, and outcome of all cases of sclerosing mesenteritis diagnosed at the Mayo Clinic, Rochester, from 1982-2005. Ninety-two cases were identified; 70% were male, with a median age of 65 years (interquartile range, 55-72). Common presenting symptoms included abdominal pain in 70%, diarrhea in 25%, and weight loss in 23%. Treatment included medical therapy alone in 26%, surgery alone in 13%, surgery followed by medical therapy in 9%, and 52% received no treatment. Ten percent responded to surgery alone, 20% responded to additional medical treatment after surgery, and 38% responded to medical therapy alone. Tamoxifen in combination with prednisone was used in 20 patients, and 60% improved. Non-tamoxifen-based regimens were used in 12 patients, and 8% improved. Eighteen deaths were noted during the study period, and 17% were attributed to complications of sclerosing mesenteritis or its treatment. Although a relatively benign condition, sclerosing mesenteritis can have a prolonged debilitating course with a fatal outcome. Our results suggest that symptomatic patients might benefit from medical therapy, particularly tamoxifen and prednisone combination treatment. Long-term follow-up is needed to substantiate these results.
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              Regulating the stability of TGFbeta receptors and Smads.

              Markus Dahl, Erna Raja, Peter Lönn … (2008)
              Transforming growth factor beta (TGFbeta) controls cellular behavior in embryonic and adult tissues. TGFbeta binding to serine/threonine kinase receptors on the plasma membrane activates Smad molecules and additional signaling proteins that together regulate gene expression. In this review, mechanisms and models that aim at explaining the coordination between several components of the signaling network downstream of TGFbeta are presented. We discuss how the activity and duration of TGFbeta receptor/Smad signaling can be regulated by post-translational modifications that affect the stability of key proteins in the pathway. We highlight links between these mechanisms and human diseases, such as tissue fibrosis and cancer.
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                Author and article information

                Journal
                Journal ID (publisher-id): BPU
                Journal ID (nlm-ta): Blood Purif
                Journal ID (doi): 10.1159/issn.0253-5068
                Title: Blood Purification
                Publisher: S. Karger AG
                ISSN (Print): 0253-5068
                ISSN (Electronic): 1421-9735
                Publication date Subscription-year: 2011
                Publication date (Print): June 2011
                Publication date (Electronic): 14 January 2011
                Volume: 31
                Issue: 4
                Pages: 252-258
                Affiliations
                Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan, ROC
                Author notes
                *Kuan-Yu Hung, MD, PhD, Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 100, Taiwan (ROC), Tel. +886 2 231 234 56, ext. 3288, Fax +886 2 239 492 69, E-Mail kyhung@ntu.edu.tw
                Article
                Publisher ID: 322255 Other ID: Blood Purif 2011;31:252–258
                DOI: 10.1159/000322255
                PubMed ID: 21242678
                SO-VID: 547cb40c-3621-4ce4-a86d-c7afabc246cc
                Copyright © © 2011 S. Karger AG, Basel
                License:

                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.

                History
                Date received : 25 May 2010
                Date accepted : 16 October 2010
                Page count
                Figures: 5, Pages: 7
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: Tamoxifen,Peritoneal dialysis,Peritoneal fibrosis,Connective tissue growth factor,Animal model
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: Tamoxifen, Peritoneal dialysis, Peritoneal fibrosis, Connective tissue growth factor, Animal model

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