Cultured human endothelial cells express platelet-derived growth factor A chain.
Cultured human endothelial cells express platelet-derived growth factor A chain.
复制标题
DOI：
--
复制
发表时间：
1987
期刊：
影响因子：
--
通讯作者：
T. Collins;J. Pober;M. Gimbrone;A. Hammacher;C. Betsholtz;B. Westermark;C. Heldin
中科院分区：
文献类型：
--
作者：
T. Collins;J. Pober;M. Gimbrone;A. Hammacher;C. Betsholtz;B. Westermark;C. Heldin
参与血管壁病理生理反应的四种主要细胞类型--内皮细胞、平滑肌细胞、血小板和单核细胞/巨噬细胞--分泌血小板衍生生长因子样（PDGF样）促有丝分裂活性。关于这些活性的大量结构数据仅存在于由血小板产生的有丝分裂原中，有丝分裂原是由不同基因编码的结构相关的A和B多肽链组成的30 kd二聚体蛋白。以前证实，正常培养的内皮细胞从c-sis基因转录编码PDGF的B链的mRNA。这里显示了由培养的血管内皮细胞产生的有丝分裂原的几个新的结构特征。正常培养的人脐静脉内皮细胞（HUVE）RNA的杂交分析显示，它们含有三种PDGF A链转录本。这些RNA种类与先前在来自两个人肿瘤细胞系的RNA中鉴定的三种RNA种类共迁移，并且似乎具有相同的相对丰度。在牛主动脉内皮细胞株或人皮肤成纤维细胞的RNA中未发现A链转录本。HUVE中的A链转录本与B链转录本具有相同的相对丰度。免疫沉淀的代谢标记的内皮细胞条件培养基与抗PDGF抗血清揭示了一个31 kd的物种，这是分裂的减少和烷基化成两个物种的16.5和17 kd。因此，内皮细胞分泌与PDGF抗原相关的二聚体促分裂原，其结构与先前分离的PDGF A链同源二聚体相同。这些发现与人内皮细胞分泌PDGF可能独立于B链表达的可能性一致。
Four principal cell types involved in the pathophysiologic response of the vessel wall--endothelial cells, smooth muscle cells, platelets, and monocyte/macrophages--secrete platelet-derived growth factor-like (PDGF-like) mitogenic activities. Extensive structural data on these activities exist only for the mitogen produced by platelets, which is a 30-kd dimeric protein composed of structurally related A and B polypeptide chains encoded by different genes. It was previously demonstrated that normal cultured endothelial cells transcribe mRNA encoding the B chain of PDGF from the c-sis gene. Here several new structural features of the mitogen produced by cultured vascular endothelial cells are shown. Hybridization analysis of RNA from normal cultured human umbilical vein endothelial (HUVE) cells revealed that they contain three PDGF A chain transcript species. These RNA species comigrated with and appeared to have the same relative abundance as the three RNA species previously identified in RNA from two human tumor cell lines. A chain transcripts were not identified in RNA from a strain of bovine aortic endothelial cells or in human dermal fibroblasts. The A chain transcripts in HUVE had the same relative abundance as the B chain transcripts. Immunoprecipitation of metabolically labeled endothelial conditioned medium with anti-PDGF antiserum revealed a 31-kd species which was split by reduction and alkylation into two species of 16.5 and 17 kd. Thus, endothelial cells secrete a dimeric mitogen antigenically related to PDGF, with a structure identical to previously isolated PDGF A-chain homodimer. These findings are consistent with the possibility that secretion of PDGF by human endothelial cells may be regulated independently of B-chain expression.