Mitogenic effect of transforming growth factor beta 1 on human fibroblasts involves the induction of platelet-derived growth factor alpha receptors.
Platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta), potent modulators of mesenchymal cell growth and differentiation, are often colocalizable in vivo. Previous in vitro studies in fibroblastic cell lines have shown variable, even antagonistic effects of TGF-beta on the mitogenic action of PDGF. This study demonstrates that in diploid human dermal fibroblasts, TGF-beta 1 is weakly mitogenic in the absence of serum or purified growth factors, and that TGF-beta 1 potentiates DNA synthesis in PDGF-stimulated fibroblasts with delayed kinetics when compared to stimulation with PDGF alone. TGF-beta 1 enhances mitogenic potency of all three PDGF isoforms and increases receptor binding of both 125I PDGF-AA and 125I PDGF-BB, consistent with the increased expression of the alpha type PDGF receptor. The induction of PDGF alpha receptor subunits by TGF-beta may play a role in enhancing the proliferative potential of human fibroblasts in certain physiologic and pathologic conditions.
Ishikawa
O
O
Department of Medicine, Medical University of South Carolina, Charleston 29425.
LeRoy
E C
EC
Trojanowska
M
M
D004261:DNA Replication; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000502:physiology; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D017479:Receptors, Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta / Q000502:physiology*
D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor