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

✍ Scribed by D. J. Hill; A. J. Strain; S. F. Elstow; I. Swenne; R. D. G. Milner

• Publisher: John Wiley and Sons
• Year: 1986
• Tongue: English
• Weight: 996 KB
• Volume: 128
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041280226

✦ Synopsis

We investigated the influence of transforming growth factor-@ (TCF-0) 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-@ had no action on thymidine incorporation. However, in the presence of 0.1% v/v fetal calf serum, TGF-@ exhibited a bi-functional action on the cells. A dose-dependent stimulation of 13H] 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 nglml. For fibroblasts from fetuses of 100 g or greater body weight, TGF-@ 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 TCF-@ 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-@ when stimulated by SM-C/ICF 1. The ability of TGF-@ to modulate I3H] thymidine incorporation did not involve a change in the time required for growth-restricted cells to enter the S phase of t h e replication cycle. These data suggest that TGF-@ 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.