Reduced syndecan-4 expression in arterial smooth muscle cells with enhanced proliferation.
Syndecans, a family of cell surface heparan sulfate (HS) containing proteoglycans (PGs), are known regulators of many biological processes including inhibition of smooth muscle cell (SMC) proliferation. Cultured arterial SMCs from atherosclerosis-susceptible White Carneau (WC) pigeons have increased proliferation rates and significant reductions in total cell-surface HS relative to atherosclerosis-resistant Show Racer (SR) SMC. Using a specific syndecan-4 cDNA, 1.5- to 2.0-fold reductions in gene expression were observed in WC SMC compared to SR SMC. Immunolocalization studies demonstrated reduced cell surface syndecan-4 protein in WC cells. Gene induction demonstrated that the reduction in syndecan-4 expression in WC cells was not due to reduced mRNA stability. Studies using cycloheximide to superinduce gene expression indicated transcriptional suppression of syndecan-4 in WC cells. The results suggest that reduced cell surface HS PG in WC arterial SMC can be explained, in part, by reductions in syndecan-4 gene expression. Differential transcriptional regulation of syndecan-4 in WC and SR cells provides a system to explore regulation of the syndecan-4 gene as well as the potential mechanisms by which syndecan-4 can exert a specific antiproliferative effect.
Bortoff
Katherine D
KD
Department of Pathology, The Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Wagner
William D
WD
D000818:Animals; D001013:Aorta, Thoracic; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D010856:Columbidae; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004195:Disease Models, Animal; D015870:Gene Expression; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013045:Species Specificity; D053671:Syndecan-4
D008562:Membrane Glycoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; D053671:Syndecan-4; D004247:DNA; D003513:Cycloheximide