Asbestos upregulates expression of the urokinase-type plasminogen activator receptor on mesothelial cells.

Content Provider	Semantic Scholar
Author	Broaddus, Virginia Courtney Sreerama Shetty Hamilton, Stanley H. Idell, Steven
Copyright Year	1999
Abstract	Inhalation of asbestos is associated with pathologic changes in the pleural space, including pleural thickening, pleural plaques, and mesothelioma. These processes are characterized by altered local proteolysis, cellular proliferation, and cell migration, suggesting that the urokinase-type plasminogen activator receptor (uPAR) could be involved in the pathogenesis of asbestos-induced pleural disease. We hypothesized that mesothelial cell uPAR expression is induced by exposure to asbestos. To test this hypothesis, we used complementary techniques in rabbit and human mesothelial cells to determine whether uPAR expression is altered by exposure to asbestos. uPAR expression was induced by chrysotile and crocidolite asbestos, but not by wollastonite, as indicated by binding of radiolabeled urokinase-type plasminogen activator (uPA) to rabbit or human mesothelial cells. uPA was not induced by fiber exposure. Exposure to exogenous uPA increased uPA activity of cells exposed to wollastonite but not asbestos-treated MeT5A cells. uPAR expression increased further when asbestos was preincubated with vitronectin (VN) or serum. Increases in uPAR expression were confirmed by binding of uPA to uPAR in cell membrane preparations and immunofluorescent staining of uPAR at the cell surface, and were associated with increases in steady-state uPAR messenger RNA. Mesothelial cell uPAR expression was also induced by media from monocytes cultured with asbestos incubated with VN and serum. By antibody neutralization, the latter effect appeared to be in part mediated by transforming growth factor-beta. We found that asbestos increases uPAR at the surface of rabbit and human mesothelial cells, suggesting that altered expression of this receptor could be involved in asbestos-induced remodeling of the pleural mesothelium.
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Alternate Webpage(s)	http://ajrcmb.atsjournals.org/content/21/5/637.full.pdf
Alternate Webpage(s)	http://intl-ajrcmb.atsjournals.org/content/21/5/637.full.pdf
PubMed reference number	10536123v1
Volume Number	21
Issue Number	5
Journal	American journal of respiratory cell and molecular biology
Language	English
Access Restriction	Open
Subject Keyword	Asbestos Asbestos, Crocidolite Cell Proliferation Chrysotile Hyperplasia Mesothelial cell Mesothelioma Mesothelium of pleura Neutralization (Chemistry) Plasma membrane Pleural Diseases Pleural cavity Senile Plaques Staining method Tissue fiber Transforming Growth Factor beta Transforming Growth Factors Urokinase Plasminogen Activator Receptor VTN gene Wollastonite incubated
Content Type	Text
Resource Type	Article