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Djafarzadeh, R.* ; Sauter, M.* ; Notohamiprodjo, S.* ; Nößner, E. ; Goyal, P.* ; Siess, W.* ; Wörnle, M.* ; Ribeiro, A.* ; Himmelein, S.* ; Sitter, T.* ; Nelson, P.J.*

Recombinant GPI-anchored TIMP-1 stimulates growth and migration of peritoneal mesothelial cells.

PLoS ONE 7:e33963 (2012)
Verlagsversion Volltext DOI PMC
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Background: Mesothelial cells are critical in the pathogenesis of post-surgical intraabdominal adhesions as well as in the deterioration of the peritoneal membrane associated with long-term peritoneal dialysis. Mesothelial denudation is a pathophysiolocigally important finding in these processes. Matrix metalloproteinase (MMP) biology underlies aspects of mesothelial homeostasis as well as wound repair. The endogenous tissue inhibitors of metalloproteinases (TIMPs) moderate MMP activity. Methods and Finding: By modifying human TIMP-1 through the addition of a glycosylphosphatidylinositol (GPI) anchor, a recombinant protein was generated that efficiently focuses TIMP-1 on the cell surface. Treatment of primary mesothelial cells with TIMP-1-GPI facilitates their mobilization and migration leading to a dramatic increase in the rate of wound experimental closure. Mesothelial cells treated with TIMP-1-GPI showed a dose dependent increase in cell proliferation, reduced secretion of MMP-2, MMP-9, TNF-alpha and urokinase-type plasminogen activator (uPA), but increased tissue plasminogen activator (t-PA). Treatment resulted in reduced expression and processing of latent TGF-beta 1. Conclusions: TIMP-1-GPI stimulated rapid and efficient in vitro wound closure. The agent enhanced mesothelial cell proliferation and migration and was bioactive in the nanogram range. The application of TIMP-1-GPI may represent a new approach for limiting or repairing damaged mesothelium.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter MATRIX METALLOPROTEINASES; FIBRINOLYTIC SYSTEM; TISSUE INHIBITORS; CAPD PATIENTS; GELATINASE-B; TGF-BETA; EXPRESSION; APOPTOSIS; CYTOKINES; ANGIOGENESIS
Sprache englisch
Veröffentlichungsjahr 2012
HGF-Berichtsjahr 2012
ISSN (print) / ISBN 1932-6203
Zeitschrift PLoS ONE
Quellenangaben Band: 7, Heft: 4, Seiten: , Artikelnummer: e33963 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort Lawrence, Kan.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501700-001
PubMed ID 22558080
DOI 10.1371/journal.pone.0033963
WOS ID WOS:000305336000008
Scopus ID 84860441448
Erfassungsdatum 2012-07-12
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