Bi‐functional action of transforming growth factor‐β on DNA synthesis in early passage human fetal fibroblasts

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Abstract
We investigated the influence of transforming growth factor‐β (TGF‐β) 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‐β had no action on thymidine incorporation. However, in the presence of 0.1% v/v fetal calf serum, TGF‐β 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‐β 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‐β on cells derived from fetuses under 50 g body weight, but inhibited on cells obtained from the larger fetuses wieghing more than 100 g. Similar results were found for changes in cell number in response to TGF‐β when stimulated by SM‐C/IGF I. The ability of TGF‐β 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‐β 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.

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