TGF-beta induces bimodal proliferation of connective tissue cells via complex control of an autocrine PDGF loop

Cell. 1990 Nov 2;63(3):515-24. doi: 10.1016/0092-8674(90)90448-n.


Transforming growth factor-beta (TGF-beta) acts as a growth inhibitor, yet it can stimulate proliferation; 1-2 fg/cell of TGF-beta 1 elicits maximal proliferation of dense and sparse cultured smooth muscle cells (SMCs), whereas higher amounts are less stimulatory. This bimodal response is not limited to SMCs, as TGF-beta induces a similar response in human fibroblasts and chondrocytes. The amount of TGF-beta 1 per cell that induces maximal proliferation is identical for dense and sparse SMCs. At low concentrations of TGF-beta, there is a 10-12 hr delay in DNA synthesis compared with that elicited by PDGF. PDGF-AA is detected in the culture medium at 24 hr, and anti-PDGF IgG blocks DNA synthesis. At higher concentrations, TGF-beta 1 decreases transcripts and expression of PDGF receptor alpha subunits. Hence, TGF-beta induces proliferation of connective tissue cells at low concentrations by stimulating autocrine PDGF-AA secretion, which at higher concentrations of TGF-beta, is decreased by down-regulation of PDGF receptor alpha subunits and perhaps by direct growth inhibition.

Publication types

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

MeSH terms

  • Aorta, Thoracic / cytology
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / metabolism
  • Cartilage / cytology*
  • Cartilage / drug effects
  • Cartilage / metabolism
  • Cell Division / drug effects
  • Cells, Cultured
  • DNA Replication / drug effects*
  • Humans
  • Infant, Newborn
  • Macromolecular Substances
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Platelet-Derived Growth Factor / biosynthesis*
  • Receptors, Cell Surface / biosynthesis*
  • Receptors, Cell Surface / genetics
  • Receptors, Platelet-Derived Growth Factor
  • Transcription, Genetic / drug effects
  • Transforming Growth Factor beta / pharmacology*


  • Macromolecular Substances
  • Platelet-Derived Growth Factor
  • Receptors, Cell Surface
  • Transforming Growth Factor beta
  • Receptors, Platelet-Derived Growth Factor