Density-dependent inhibitory effect of transforming growth factor-β on human fibroblasts involves the down-regulation of platelet-derived growth factor α-receptors

✍ Scribed by Y. Paulsson; C. Karlsson; C.-H. Heldin; B. Westermark

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 812 KB
• Volume: 157
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041570113

✦ Synopsis

Abstract

We have previously found that transforming growth factor‐β1 (TGF‐β1) inhibits the mitogenic activity of platelet‐derived growth factor (PDGF) in cultures of human neonatal fibroblasts in a density‐dependent fashion. In the present investigation we determined the effect of TGF‐β1 on the PDGF α‐receptor, which binds all PDGF isoforms, as well as on the β‐receptor, which binds only PDGF‐BB with high affinity. We found that the inhibitory effect of TGF‐β1 on PDGF‐AA‐induced mitogenesis was density‐dependent; when dense cell cultures were preincubated with TGF‐β1, there was an complete inhibition of ^3^H‐thymidine incorporation, whereas the effect was less in sparse cultures. A similar density‐dependent effect of TGF‐β1 was seen in PDGF‐BB treated cells, although less pronounced. The binding of ^125^I‐labeled PDGF‐AA and PDGF‐BB to the α‐receptor was significantly reduced after treatment with TGF‐β1 in dense cultures, whereas the sparse cultures were less affected. A decrease of α‐receptor mRNA was also seen. The levels of β‐receptor protein and mRNA were unaffected. We conclude that the growth inhibitory effect of TGF‐β1 is cell density‐dependent and involves down‐regulation of PDGF α‐receptors. © 1993 Wiley‐Liss, Inc.