Transforming growth factor β1‐mediated inhibition of smooth muscle cell proliferation is associated with a late G1 cell cycle arrest
Tóm tắt
The effect of transforming growth factor β1 (TGFβ1) on the proliferative response of aortic smooth muscle cells (SMC) in vitro was investigated. TGFβ1 substantially inhibited the growth of human and bovine SMC. Rapidly growing SMC and quiescent serum‐stimulated SMC were inhibited by TGFβ1 with an ID50 of approximately 0.5 ng/ml and maximal inhibition was observed at 10 ng/ml TGFβ1. In the presence of TGFβ1, 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 TGFβ1 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 TGFβ1 has no effect on the transcription or translation of p34cdc2. Under these growth inhibitory conditions, TGFβ1 is still capable of upregulating the expression of fibronectin mRNA. These results suggest that TGFβ1 growth inhibition in SMC is associated with the regulation of p34cdc2 activity in late G1. © 1993 Wiley‐Liss, Inc.
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Tài liệu tham khảo
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