The mechanism through which growth factors cause glycosaminoglycan (GAG) hyper-elongation is unclear. We have investigated the role of transcription and translation on the GAG hyper-elongation effect of plateletderived growth factor (PDGF) in human vascular smooth muscle cells (VSMCs). To determine if the response involves specific signalling pathways or the process of GAG hyper-elongation we have also investigated the effects of epidermal growth factor (EGF), transforming growth factor-β (TGF-β) and thrombin. We report that both actinomycin D and cycloheximide completely abolished the ability of PDGF to stimulate radiosulphate incorporation and GAG elongation into secreted proteoglycans, and to increase the size of xyloside GAGs. Blocking de novo protein synthesis completely prevented the action of all growth factors tested to elongate GAG chains. These results lay a foundation for further investigation into the genes and proteins implicated in this response.
- Actinomycin D
- Vascular smooth muscle cells