Vascular endothelial growth factor. Regulation by cell differentiation and activated second messenger pathways.
Vascular endothelial growth factor. Regulation by cell differentiation and activated second messenger pathways.
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DOI：
10.1016/s0021-9258(18)42003-0
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发表时间：
1992-08
期刊：
影响因子：
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通讯作者：
K. Claffey;W. Wilkison;B. Spiegelman
中科院分区：
文献类型：
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作者：
K. Claffey;W. Wilkison;B. Spiegelman
血管内皮生长因子 (VEGF) 是一种血管生成多肽，已从多种致瘤和非转化细胞系中分离出来。由于血管生长对细胞和组织发育的重要性，我们检查了多种小鼠组织和啮齿动物细胞分化模型中的 VEGF 基因表达。使用克隆的鼠 VEGF cDNA，我们发现 VEGF mRNA 在许多成年小鼠组织中以相对较低的水平表达。然而，该信息在两种细胞分化模型中显着诱导：3T3-脂肪转化和C2C12肌源性分化。脂肪细胞分化过程中也会诱导 VEGF 蛋白分泌。 VEGF mRNA 在嗜铬细胞瘤 (PC12) 细胞转化和分化模型中受到显着调节。转化的未分化细胞表达中等水平的 VEGF mRNA，并且当细胞分化为非恶性神经元样细胞时，这种表达实际上消失。使用佛波酯和 cAMP 类似物的实验表明，前脂肪细胞中 VEGF mRNA 的表达受到蛋白激酶 C 和蛋白激酶 A 介导的途径的刺激。这些结果表明，VEGF mRNA 水平与细胞分化过程密切相关。他们还清楚地证明，这种血管生成因子的表达在转化的细胞系中受到特异性调节，可能是通过细胞第二信使途径的异常激活。
Vascular endothelial growth factor (VEGF) is an angiogenic polypeptide that has been isolated from a variety of tumorigenic and nontransformed cell lines. Because of the importance of blood vessel growth to cell and tissue development, we have examined VEGF gene expression in a variety of mouse tissues and rodent models of cellular differentiation. Using a cloned murine VEGF cDNA we show that VEGF mRNA is expressed at relatively low levels in many adult mouse tissues examined. However, this message is dramatically induced in two models of cell differentiation: 3T3-adipose conversion and C2C12 myogenic differentiation. VEGF protein secretion is also induced in adipocyte differentiation. VEGF mRNA is markedly regulated in a pheochromocytoma (PC12) cell model of transformation and differentiation. The transformed undifferentiated cells express moderate levels of VEGF mRNA and this expression is virtually extinguished when cells differentiate into non-malignant neuron-like cells. Experiments employing phorbol esters and cAMP analogues indicate that VEGF mRNA expression is stimulated in preadipocytes by both protein kinase C and protein kinase A-mediated pathways. These results suggest that VEGF mRNA levels are closely linked to the process of cellular differentiation; they also clearly demonstrate that expression of this angiogenic factor is specifically regulated in a transformed cell line, possibly via aberrant activation of cellular second messenger pathways.