THE EXTRACELLULAR GLYCOPROTEIN SPARC INTERACTS WITH PLATELET-DERIVED GROWTH-FACTOR (PDGF)-AB AND (PDGF)-BB AND INHIBITS THE BINDING OF PDGF TO ITS RECEPTORS
THE EXTRACELLULAR GLYCOPROTEIN SPARC INTERACTS WITH PLATELET-DERIVED GROWTH-FACTOR (PDGF)-AB AND (PDGF)-BB AND INHIBITS THE BINDING OF PDGF TO ITS RECEPTORS
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DOI：
10.1073/pnas.89.4.1281
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发表时间：
1992-02-15
影响因子：
11.1
通讯作者：
SAGE, EH
中科院分区：
文献类型：
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作者：
RAINES, EW;LANE, TF;SAGE, EH
生长因子、细胞和细胞外基质之间的相互作用对于调节与发育、伤口愈合和病理过程相关的定向细胞迁移和增殖至关重要。在这里，我们报告的协会PDGF-AB和-BB，但不是PDGF-AA，与细胞外糖蛋白β。复合物的β-环糊精和I-125标记的PDGF-BB或-AB特异性免疫沉淀的抗β-环糊精免疫球蛋白。I-125-PDGF-BB和-AB也特异性结合于固定在微量滴定威尔斯孔上或在从SDS/聚丙烯酰胺凝胶转移后结合于硝酸纤维素的底物。PDGF-BB与PDGF-BB的结合是pH依赖性的;仅在pH 6.6以上才能检测到显著的结合。SPARC与特定二聚体形式的PDGF的相互作用影响了该有丝分裂原的活性。PDGF-BB和PDGF-AB，但不PDGF-AA，以剂量依赖性方式抑制人皮肤成纤维细胞的结合。VEGF和PDGF在大多数正常成人组织中的表达是最小的，但在损伤后增加。PDGF-B链和TGF-β 1在动脉粥样硬化晚期病变中表达增强。我们认为，协调表达的血管损伤后，PDGF和PDGF-B的二聚体可能会调节活性的特定的二聚体形式的PDGF在体内。
Interactions among growth factors, cells, and extracellular matrix are critical to the regulation of directed cell migration and proliferation associated with development, wound healing, and pathologic processes. Here we report the association of PDGF-AB and -BB, but not PDGF-AA, with the extracellular glycoprotein SPARC. Complexes of SPARC and I-125-labeled PDGF-BB or -AB were specifically immunoprecipitated by anti-SPARC immunoglobulins. I-125-PDGF-BB and -AB also bound specifically to SPARC that was immobilized on microtiter wells or bound to nitrocellulose after transfer from SDS/polyacrylamide gels. The binding of PDGF-BB to SPARC was pH-dependent; significant binding was detectable only above pH 6.6. The interaction of SPARC with specific dimeric forms of PDGF affected the activity of this mitogen. SPARC inhibited the binding of PDGF-BB and PDGF-AB, but not PDGF-AA, to human dermal fibroblasts in a dose-dependent manner. The expression of SPARC and PDGF was minimal in most normal adult tissues but was increased after injury. Enhanced expression of both PDGF-B chain and SPARC was seen in advanced lesions of atherosclerosis. We suggest that the coordinate expression of SPARC and PDGF-B-containing dimers following vascular injury may regulate the activity of specific dimeric forms of PDGF in vivo.