Growth factor-mediated hyper-elongation of glycosaminoglycan chains on biglycan requires transcription and translation.
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 platelet-derived 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-beta (TGF-beta) 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.
Yang
Sundy N Y
SN
BakerIDI Heart and Diabetes Institute, Diabetes and Cell Biology Laboratory, Melbourne, VIC, 3004, Australia.
Burch
Micah L
ML
Getachew
Robel
R
Ballinger
Mandy L
ML
Osman
Narin
N
Little
Peter J
PJ
D058578:Biglycan; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011509:Proteoglycans / Q000096:biosynthesis* / Q000235:genetics; D013462:Sulfur Radioisotopes / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C546884:BGN protein, human; D058578:Biglycan; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D011500:Protein Synthesis Inhibitors; D011509:Proteoglycans; D013462:Sulfur Radioisotopes; D016212:Transforming Growth Factor beta; D003609:Dactinomycin; D004815:Epidermal Growth Factor; D013917:Thrombin