THE EXTRACELLULAR-MATRIX AS A CELL-SURVIVAL FACTOR
THE EXTRACELLULAR-MATRIX AS A CELL-SURVIVAL FACTOR
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DOI：
10.1091/mbc.4.9.953
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发表时间：
1993-09-01
影响因子：
3.3
通讯作者：
SCHWARTZ, MA
中科院分区：
文献类型：
--
作者：
MEREDITH, JE;FAZELI, B;SCHWARTZ, MA
细胞程序性死亡(PCD)或凋亡是一种自然发生的细胞自杀途径，诱导各种类型的细胞。在许多情况下，PCD是由作为生存因素的特定激素或生长因子的停用而引起的。在这项研究中，我们研究了细胞外基质(ECM)作为细胞生存因子的潜在作用。我们的结果表明，在没有任何ECM相互作用的情况下，人内皮细胞迅速经历PCD，这是由细胞形态、核碎裂、DNA降解、蛋白质交联和PCD特异性基因TRPM-2的表达决定的。PCD可以被固定的整合素Beta1抗体上的细胞所阻断，但不能被I类组织相容性抗原(HLA)或血管细胞黏附分子-1(VCAM-1)的抗体所阻断，这表明整合素介导的信号是维持细胞活力所必需的。用酪氨酸磷酸酶抑制剂原钒酸钠处理悬浮中的细胞也能阻断PCD。当检查其他类型的细胞时，一些，但不是全部，当失去与ECM的黏附时，经历了快速的细胞死亡。这些结果表明，除了调节细胞的生长和分化外，ECM也是许多细胞类型的生存因子。
Programmed cell death (PCD) or apoptosis is a naturally occurring cell suicide pathway induced in a variety of cell types. In many cases, PCD is induced by the withdrawal of specific hormones or growth factors that function as survival factors. In this study, we have investigated the potential role of the extracellular matrix (ECM) as a cell survival factor. Our results indicate that in the absence of any ECM interactions, human endothelial cells rapidly undergo PCD, as determined by cell morphology, nuclei fragmentation, DNA degradation, protein cross-linking, and the expression of the PCD-specific gene TRPM-2. PCD was blocked by plating cells on an immobilized integrin beta1 antibody but not by antibodies to either the class I histocompatability antigen (HLA) or vascular cell adhesion molecule-1 (VCAM-1), suggesting that integrin-mediated signals were required for maintaining cell viability. Treatment of the cells in suspension with the tyrosine phosphatase inhibitor sodium orthovanadate also blocked PCD. When other cell types were examined, some, but not all, underwent rapid cell death when deprived of adhesion to the ECM. These results suggest that in addition to regulating cell growth and differentiation, the ECM also functions as a survival factor for many cell types.