Cizmeci-Smith G, Langan E, Youkey J, Showalter L J, Carey D J
Sigfried and Janet Weis Center for Research, Geisinger Clinic, Danville, Pa 17822-2613, USA.
Arterioscler Thromb Vasc Biol. 1997 Jan;17(1):172-80. doi: 10.1161/01.atv.17.1.172.
Syndecans are a family of transmembrane proteoglycans that have been implicated in cell-extracellular matrix adhesion and growth factor binding. We reported previously that syndecan-1 expression by cultured rate vascular smooth muscle cells (VSMCs) is induced by serum- or platelet-derived growth factor (PDGF). We now report that syndecan-4 mRNA is rapidly induced in cultured VSMCs in response to basic fibroblast growth factor (bFGF) or serum stimulation. In the presence of cycloheximide, induction of syndecan-4 mRNA was enhanced. These characteristics identified syndecan-4 as a primary-response gene product in VSMCs. In contrast, syndecan-1 mRNA expression in response to serum was completely blocked in the presence of cycloheximide. We also examined the expression of syndecan mRNAs in VSMCs in response to balloon catheter injury in vivo. A reverse transcriptase-polymerase chain reaction technique was developed that enabled us to amplify all four syndecan mRNAs in a single reaction tube and determine relative changes in their expression. All four syndecan mRNAs were detected in uninjured rat carotid arteries. In endothelium-denuded arteries, the medial layer (presumably VSMCs) accounted for 70% to 90% of the syndecan mRNAs in the vessel wall. The levels of syndecan-2 and syndecan-3 mRNAs were not altered significantly after balloon injury. In contrast, syndecan-4 mRNA was increased at early times after injury but then decreased to control level by 7 days. Syndecan-1 mRNA levels showed a slower but prolonged increase that reached a maximum at 7 days after injury. Immunostaining with anti-syndecan-4 antibodies demonstrated a rapid increase in syndecan-4 proteoglycan expression in the injured carotid artery.
Syndecans是一族跨膜蛋白聚糖,与细胞-细胞外基质黏附及生长因子结合有关。我们先前报道,培养的大鼠血管平滑肌细胞(VSMC)中syndecan-1的表达受血清或血小板衍生生长因子(PDGF)诱导。我们现在报道,培养的VSMC中syndecan-4 mRNA在碱性成纤维细胞生长因子(bFGF)或血清刺激后迅速被诱导。在存在放线菌酮的情况下,syndecan-4 mRNA的诱导增强。这些特征确定syndecan-4为VSMC中的一种初级反应基因产物。相反,在存在放线菌酮的情况下,血清诱导的syndecan-1 mRNA表达被完全阻断。我们还检测了体内VSMC中syndecan mRNA对球囊导管损伤的反应。开发了一种逆转录-聚合酶链反应技术,使我们能够在单个反应管中扩增所有四种syndecan mRNA,并确定它们表达的相对变化。在未损伤的大鼠颈动脉中检测到所有四种syndecan mRNA。在内皮剥脱的动脉中,中层(可能是VSMC)占血管壁中syndecan mRNA的70%至90%。球囊损伤后syndecan-2和syndecan-3 mRNA的水平没有明显改变。相反,syndecan-4 mRNA在损伤后早期增加,但在7天时降至对照水平。syndecan-1 mRNA水平显示出较慢但持续时间较长的增加,在损伤后7天达到最大值。用抗syndecan-4抗体进行免疫染色显示,损伤的颈动脉中syndecan-4蛋白聚糖表达迅速增加。