The effects and the mechanisms of action of transforming ( @entity6474 ) and basic fibroblast ( @entity540 ) growth factors on the synthesis of hyaluronan and proteoglycans (PGs) in @entity1 @entity3620 cells have been studied. Two cell lines, one with an epithelial differentiation (STAV-AB) and the other with a fibroblast-like phenotype (STAV-FCS) have been examined. Using monoclonal antibodies to growth factor receptors, the presence of a high density of the specific receptors for @entity6474 and @entity540 was immunochemically demonstrated in both @entity2615 cell lines. These cell lines synthesize hyaluronan, galactosaminoglycan containing PGs (GalAGPGs) and heparan @entity597 containing PGs (HSPGs) at different levels; the epithelial differentiated cells produce a 6-8 times higher amount than those with the fibroblast-like morphology. In both cell lines the rates of proteoglycan synthesis were affected in a dose-dependent mode by @entity6474 and @entity540 . Maximal synthetic levels of both secreted and cell-bound proteoglycans were reached at 10 ng/mL whereafter they remained constant. @entity6474 stimulated the synthesis of hyaluronan, GalAGPGs and of HSPGs in STAV-FCS, whereas this effect was pronounced only for GalAGPGs in STAV-AB. @entity540 showed stimulatory effects for the synthesis of hyaluronan and cell associated GalAGPGs in STAV-FCS, whereas no significant enhancement was recorded for HSPGs. In the STAV-AB cell line the synthesis of hyaluronan and GalAGPGs remained unaltered by the addition of both growth factors. Although the synthesis of total HSPGs remained constant, this was due to a decrease in the secreted product and a similar increase of the cell-associated proteoglycan. The stimulatory mechanisms of both growth factors was examined by using the specific protein @entity669 kinase inhibitor @entity670 . Incubation of both cell lines with this @entity24826 inhibited the enhanced synthesis of hyaluronan and all PGs induced by @entity6474 and @entity540 . It is suggested that most, if not all, of the stimulatory effects on the hyaluronan and PGs synthesis are mediated via protein @entity669 kinase activity elicited by receptor-ligand complexes. Decreased synthetic rates obtained when giving @entity670 to unstimulated @entity2615 cells may indicate the relation of hyaluronan and PGs synthesis with an autocrine stimulatory mechanisms.

Proteoglycan synthesis induced by transforming and basic fibroblast growth factors in @entity1 @entity3620 is mediated through specific receptors and the XXXX kinase intracellular pathway.

@entity1 :: ('9606', 'Species') :: ['human'] @entity24826 :: ('CHEBI:50753', 'Chemical') :: ['isoflavonoid'] @entity670 :: ('MESH:D019833', 'Chemical') :: ['genistein'] @entity2615 :: ('MESH:D008654', 'Disease') :: ['mesothelioma'] @entity540 :: ('2247', 'Gene') :: ['bFGF'] @entity3620 :: ('MESH:C562839', 'Disease') :: ['malignant mesothelioma'] @entity6474 :: ('7042', 'Gene') :: ['TGF-beta 2'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity597 :: ('CHEBI:16189', 'Chemical') :: ['sulphate']
@entity669 :: (CHEBI:18186,Chemical) :: ['tyrosine']
