Department of Pathology , University of Washington , Seattle 98195 .
Cell 63 : 515-24 ( 1990)
Abstract
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 .