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Modulation of Growth of Vascular Smooth Muscle Cells by Activin A

1993; Elsevier BV; Volume: 206; Issue: 1 Linguagem: Inglês

10.1006/excr.1993.1131

1090-2422

Itaru Kojima, Hideo Mogami, Norio Kawamura, Horoshi Yasuda, Hiroshi Shibata,

Growth Hormone and Insulin-like Growth Factors

Activin A is a homodimerie protein structurally related to transforming growth factor-β. 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 bromodeoxy-uridine occurred after a 12-h lag period. The effect of activin A on nuclear labeling was dose-dependent, being maximal at 10-9M. 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 indiente that activin A modifies growth of VSMC by complex mechanisms involving autocrine production of IGF-1 and modification of the action of IGF-1.