Modulation of growth of vascular smooth muscle cells by activin A.
Activin A is a homodimeric protein structurally related to transforming growth factor-beta. The present study was conducted to examine the effect of activin A on the growth of rat vascular smooth muscle cells (VSMC) in culture. When serum-deprived cells were incubated with activin A, nuclear labeling of bromodeoxyuridine occurred after a 12-h lag period. The effect of activin A on nuclear labeling was dose-dependent, being maximal at 10(-9) M. Activin A also increased the number of VSMC after 30 h of incubation. Insulin-like growth factor-1 (IGF-1) had only a small effect on nuclear labeling by itself but the effects of IGF-1 and activin A were additive. When quiescent VSMC were treated with activin A for 4 h, the effect of subsequent IGF-1 was markedly enhanced. Furthermore, activin A induced an autocrine production of IGF-1 in VSMC. In contrast to these positive effects on cell growth, activin A was rather inhibitory to the action of IGF-1 in activin-primed cells. In addition, activin A inhibited platelet-derived growth factor-induced nuclear labeling. These results indicate that activin A modifies growth of VSMC by complex mechanisms involving autocrine production of IGF-1 and modification of the action of IGF-1.
Kojima
I
I
Cell Biology Research Unit, Gunma University, Maebashi, Japan.
Mogami
H
H
Kawamura
N
N
Yasuda
H
H
Shibata
H
H
D028341:Activins; D000818:Animals; D001973:Bromodeoxyuridine / Q000032:analysis / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006133:Growth Substances / Q000494:pharmacology; D007265:Inhibins / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D028341:Activins; D007265:Inhibins; D007334:Insulin-Like Growth Factor I; D004247:DNA; D001973:Bromodeoxyuridine