Bi-functional action of transforming growth factor-beta on DNA synthesis in early passage human fetal fibroblasts.
We investigated the influence of transforming growth factor-beta (TGF-beta) on DNA synthesis in human fetal fibroblasts, as measured by the incorporation of [3H]thymidine and cell replication. In serum-free medium, without additional peptide growth factors, TGF-beta had no action on thymidine incorporation. However, in the presence of 0.1% v/v fetal calf serum, TGF-beta exhibited a bi-functional action on the cells. A dose-dependent stimulation of [3H]thymidine incorporation, and an increase in cell number, occurred with fibroblasts established from fetuses under 50 g body weight, with a maximum stimulation seen at 1.25 ng/ml. For fibroblasts from fetuses of 100 g or greater body weight, TGF-beta caused a dose-related decrease in thymidine uptake with a maximal inhibition at 2.5 ng/ml, and a small decrease in cell number. When DNA synthesis was stimulated by the addition of somatomedin-C/insulin-like growth factor I, epidermal growth factor, or platelet-derived growth factor, their actions were potentiated by the presence of TGF-beta on cells derived from fetuses under 50 g body weight, but inhibited on cells obtained from the larger fetuses weighing more than 100 g. Similar results were found for changes in cell number in response to TGF-beta when stimulated by SM-C/IGF I. The ability of TGF-beta to modulate [3H] thymidine incorporation did not involve a change in the time required for growth-restricted cells to enter the S phase of the replication cycle. These data suggest that TGF-beta may exert either a growth-promoting or growth-inhibiting action on human fetal connective tissues in the presence of other peptide growth factors, which is dependent on fetal age and development.
D001835:Body Weight; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005333:Fetus / Q000166:cytology* / Q000378:metabolism; D005347:Fibroblasts; D005865:Gestational Age; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D015291:Transforming Growth Factors
D010455:Peptides; D010982:Platelet-Derived Growth Factor; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D015291:Transforming Growth Factors; D004247:DNA; D013936:Thymidine