Transforming growth factor beta 1-mediated inhibition of smooth muscle cell proliferation is associated with a late G1 cell cycle arrest.

The effect of transforming growth factor beta 1 (TGF beta 1) on the proliferative response of aortic smooth muscle cells (SMC) in vitro was investigated. TGF beta 1 substantially inhibited the growth of human and bovine SMC. Rapidly growing SMC and quiescent serum-stimulated SMC were inhibited by TGF beta 1 with an ID50 of approximately 0.5 ng/ml and maximal inhibition was observed at 10 ng/ml TGF beta 1. In the presence of TGF beta 1, quiescent serum-stimulated SMC progress into the G1 phase of the cell cycle, but become reversibly arrested at a point temporally located 1-2 hours from S phase. Release from this late G1 TGF beta 1 arrest point results in S phase entry within 2 hours. Associated with this inhibitory effect is a decrease in the histone H1 kinase activity of p34cdc2 protein kinase while TGF beta 1 has no effect on the transcription or translation of p34cdc2. Under these growth inhibitory conditions, TGF beta 1 is still capable of upregulating the expression of fibronectin mRNA. These results suggest that TGF beta 1 growth inhibition in SMC is associated with the regulation of p34cdc2 activity in late G1.