| The John F. Maher Recipient Lecture 2004: Rage in the peritoneum. | |
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MedLine Citation:
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PMID: 15770917 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Several conditions in the peritoneal membrane of peritoneal dialysis (PD) patients promote the accumulation of advanced glycation end-products (AGEs), that is, the uremic state, exposure to high glucose concentrations, and exposure to glucose degradation products (GDPs). AGEs exert some of their biologic actions through binding with a cell surface receptor, termed RAGE. Interaction of AGEs with RAGE induces sustained cellular activation, including the production of the fibrogenic growth factor, transforming growth factor-beta (TGF-beta). TGF-beta is pivotal in the process of epithelial-to-mesenchymal transition, through which cells of epithelial origin acquire myofibroblastic characteristics. Myofibroblasts are involved in virtually all conditions of pathological fibrosis. Submesothelial fibrosis is an important feature in peritoneal biopsies of PD patients, especially of those with clinical problems. We therefore examined the role of RAGE in peritoneal fibrosis, in an animal model of uremia, of high glucose exposure, and of peritoneal dialysate exposure. All three models were characterized by accumulation of AGEs, upregulation of RAGE, and fibrosis. Antagonism of RAGE prevented the upregulation of TGF-beta and fibrosis in the peritoneal membrane. We further examined the underlying mechanism of peritoneal fibrosis in the uremic model. Prominent myofibroblast transdifferentiation of mesothelial cells was identified by co-localization of cytokeratin and alpha-smooth muscle actin in submesothelial and interstitial fibrotic tissue. Antagonism of RAGE prevented conversion of mesothelial cells to myofibroblasts in uremia. In conclusion, we hypothesize that accumulation of AGEs in the peritoneal membrane, as a consequence of the uremic environment, chronic exposure to high glucose, and exposure to GDPs, results in an increased expression of RAGE. The interaction of AGEs with RAGE induces peritoneal fibrosis by virtue of upregulation of TGF-beta and subsequent conversion of mesothelial cells into myofibroblasts. |
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Authors:
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An S De Vriese |
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Publication Detail:
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Type: Lectures |
Journal Detail:
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Title: Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis Volume: 25 ISSN: 0896-8608 ISO Abbreviation: Perit Dial Int Publication Date: 2005 Jan-Feb |
Date Detail:
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Created Date: 2005-03-17 Completed Date: 2005-07-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8904033 Medline TA: Perit Dial Int Country: Canada |
Other Details:
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Languages: eng Pagination: 8-11 Citation Subset: IM |
Affiliation:
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Renal Unit, University Hospital Gent, Belgium. an.devriese@azbrugge.be |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Dialysis Solutions
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adverse effects,
chemistry Fibrosis / etiology*, physiopathology Glycosylation End Products, Advanced / physiology* Humans Peritoneal Dialysis / adverse effects* Peritoneum / pathology*, physiopathology Receptors, Immunologic / physiology* Uremia / physiopathology, therapy |
| Chemical | |
Reg. No./Substance:
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0/Dialysis Solutions; 0/Glycosylation End Products, Advanced; 0/Receptors, Immunologic; 0/advanced glycosylation end-product receptor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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