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.
Reddy
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KB
Department of Cell Biology (NC-1), Cleveland Clinic Research Foundation, Ohio 44195.
Howe
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PH
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002417:Cattle; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D006656:Protamine Kinase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016326:Extracellular Matrix Proteins; D006131:Growth Inhibitors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D006656:Protamine Kinase; D016203:CDC2 Protein Kinase