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 10-10,000 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.
Morisaki
N
N
Second Department of Internal Medicine, School of Medicine, Chiba University, Japan.
Kawano
M
M
Koyama
N
N
Koshikawa
T
T
Umemiya
K
K
Saito
Y
Y
Yoshida
S
S
D000818:Animals; D001013:Aorta, Thoracic; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005312:Fetal Blood; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D015151:Immunoblotting; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D011817:Rabbits; D013489:Suppression, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D016271:Proto-Oncogene Proteins c-myc; D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors; D004247:DNA