EFFECTS OF TRANSFORMING GROWTH FACTOR-BETA-1 ON GROWTH OF AORTIC SMOOTH-MUSCLE CELLS - INFLUENCES OF INTERACTION WITH GROWTH-FACTORS, CELL STATE, CELL PHENOTYPE, AND CELL-CYCLE

Transforming growth factor (TGF)-beta-1 may have different effects on cell proliferation depending on many conditions. This paper clarifies the effects of various conditions on the effect of TGF-beta-1 on proliferation of cultured rabbit aortic smooth muscle cells (SMC) and also the time of its action during the cell cycle. TGF-beta-1 at 10-10000 pg/ml inhibited DNA synthesis of SMC in the G0 stage derived from normal media or atheromatous intima stimulated by either platelet-derived growth factor (PDGF), fibroblast growth factor, SMC-derived growth factor, or fetal bovine serum (FBS). TGF-beta-1 also inhibited the growth of SMC in the growing state stimulated by either PDGF or FBS. TGF-beta-1 was effective only when added to the culture within 2 h after stimulation of the G0 state SMC with PDGF. It also inhibited increase in transcription of the c-myc protooncogene on stimulation of SMC with PDGF. These data suggest that TGF-beta-1 inhibited proliferation of SMC irrespective of the cell phenotype, growth conditions, and growth factors present and that it exerted this inhibitory effect during the time of the G0/G1 transition.