Transforming growth factor beta is a modulator of platelet-derived growth factor action in vascular smooth muscle cells: a possible role for catalase activity and glutathione peroxidase activity.
Transforming growth factor-beta (TGF-beta) has been implicated in mediating the growth of vascular smooth muscle cells (VSMCs) after vascular injury. In this study, we examined the mechanism underlying the growth-modulating effects of TGF-beta in confluent VSMCs. Stimulation of rat VSMC by TGF-beta decreased both their catalase activity and glutathione peroxidase activity in a dose-dependent manner. In mitogenesis assays using the confluent cells, TGF-beta was not a direct mitogen for VSMC, but potentiated the stimulatory effect of platelet-derived growth factor (PDGF)-BB. This enhancement of mitogenesis was blunted by the addition of the scavenging enzyme catalase or the chemical antioxidant N-acetyl-L-cysteine. In summary, TGF-beta enhances the mitogenic effect response of PDGF-BB, largely depending on the dysregulation of catalase activity and glutathione peroxidase activity by TGF-beta.
Nishio
E
E
Department of Pharmacology, National Defense Medical College, Saitama, Japan.
Watanabe
Y
Y
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism*; D002478:Cells, Cultured; D005979:Glutathione Peroxidase / Q000378:metabolism*; D008934:Mitogens / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014316:Tritium
D000975:Antioxidants; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D014316:Tritium; D002374:Catalase; D005979:Glutathione Peroxidase; D013936:Thymidine