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

J Cell Physiol. 1993 Jul;156(1):48-55. doi: 10.1002/jcp.1041560108.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CDC2 Protein Kinase / metabolism
  • Cattle
  • Cell Cycle*
  • Cell Division / drug effects
  • Cells, Cultured
  • Extracellular Matrix Proteins / genetics
  • Gene Expression / drug effects
  • Growth Inhibitors / pharmacology*
  • Humans
  • In Vitro Techniques
  • Muscle, Smooth, Vascular / cytology*
  • Protamine Kinase / metabolism
  • RNA, Messenger / genetics
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Extracellular Matrix Proteins
  • Growth Inhibitors
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Protamine Kinase
  • CDC2 Protein Kinase