Enhanced expression of plasminogen activator inhibitor-1 by dedifferentiated thyrocytes.
Porcine thyrocytes in vitro in the presence of TSH adopt follicular-like morphology. Epidermal growth factor, phorbol esters or transforming growth factor beta-1 (TGFbeta-1) induce a rapid spreading of the cells and dedifferentiation. In addition to thyroglobulin, dedifferentiated thyrocytes secreted into the culture medium three proteins in abundant quantities. Two of them have been previously identified as thrombospondin-1 and clusterin, respectively. Using the microsequencing method we identified the third one, a M(r) 45,000 glycosylated protein, as plasminogen activator inhibitor-1 (PAI-1). EGF, phorbol esters or TGF-beta1 predominantly increased PAI-1 protein expression in TSH-treated cells. The maximal increase of PAI-1 mRNA steady-state level was observed 6 h after EGF treatment and sustained up to 48 h. Recombinant PAI-1 inhibited cell-associated plasmin activity and delayed cell spreading. Enhanced synthesis and secretion of PAI-1 upon treatment with different growth factors during dedifferentiation process and spreading may be considered a feed-back defence mechanism of the cells to harmful extracellular stimuli.
Kotlarz
Grazyna
G
Laboratoire de Biochimie, CNRS FRE 2534, Faculté de Médecine, IFR 53, 51 095 Reims Cedex, France.
Wegrowski
Yanusz
Y
Martiny
Laurent
L
Declerck
Paul J
PJ
Bellon
Georges
G
D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004815:Epidermal Growth Factor / Q000378:metabolism; D010703:Phorbol Esters / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013552:Swine; D013961:Thyroid Gland / Q000166:cytology*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014357:Trypsin / Q000494:pharmacology
D018076:DNA, Complementary; D010703:Phorbol Esters; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004815:Epidermal Growth Factor; D014357:Trypsin