Glycosylphosphatidylinositol (GPI) hydrolysis by transforming growth factor-beta1 (TGF-beta1) as a potential early step in the inhibition of epithelial cell proliferation.
Glycosylphosphatidylinositol (GPI) was previously identified in rabbit articular chondrocytes as being a precursor of inositolphosphate glycan (IPG), released upon (Transforming Growth Factor-beta) (TGF-beta) exposure, and capable of mimicking the proliferative effects of the growth factor. Here, using mink lung epithelial cells (CCL 64), which are known to be growth-inhibited by TGF-beta, we studied the potential role of GPI-derived molecules in the antiproliferative effect of TGF-beta1. We first identified an endogenous pool of GPI material and three different anionic forms of IPG in epithelial cells pre-labeled with [3H]glucosamine. Shortly (8 min) after TGF-beta1 addition, the cells responded by a rapid and transient hydrolysis of GPI, accompanied by the release of the most anionic form of IPG. This TGF-beta-released IPG, after partial purification, was shown to decrease the proliferation of CCL 64 cells. Moreover, anti-IPG antibodies reduced the effects of TGF-beta and blocked the effects of partially purified IPG. These data strongly suggest that GPI hydrolysis may be an early step of the TGF-beta signalling pathway involved in growth inhibition of epithelial cells.
Laboratoire de Biochimie du Tissu Conjonctif, Faculté de Médecine, CHU Côte de Nacre, Caen, France.
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Bogdanowicz
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JP
Pujol
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D005944:Glucosamine / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000302:isolation & purification / Q000378:metabolism*; D006868:Hydrolysis; D007295:Inositol Phosphates; D008168:Lung / Q000166:cytology*; D008563:Membrane Lipids / Q000737:chemistry; D008907:Mink; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism*; D011134:Polysaccharides; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D014316:Tritium / Q000378:metabolism
D017261:Glycosylphosphatidylinositols; D007295:Inositol Phosphates; D008563:Membrane Lipids; D009844:Oligosaccharides; D011134:Polysaccharides; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C028039:inositol phosphate glycan; D014316:Tritium; D004247:DNA; D005944:Glucosamine