Control of smooth muscle cell proliferation and phenotype by integrin signaling through focal adhesion kinase
Control of smooth muscle cell proliferation and phenotype by integrin signaling through focal adhesion kinase
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DOI：
10.1006/bbrc.2000.2769
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发表时间：
2000-05-27
影响因子：
3.1
通讯作者：
Mogford, JE
中科院分区：
文献类型：
--
作者：
Morla, AO;Mogford, JE
细胞外基质蛋白如纤连蛋白（FN）和层粘连蛋白（LM）已知有助于控制血管平滑肌细胞（VSMC）的生长和表型。在这里，我们分析了VSMCs中生长因子和整合素信号通路之间的关系。培养猪冠状动脉平滑肌细胞（PCASMCs）FN和LM导致细胞增殖和收缩蛋白的表达不同的影响。无论用于支持增殖的生长因子如何，在FN上培养的PCASMC的增殖速率高于在LM上培养的细胞。此外，在LM上培养的细胞显示出比在FN上培养的细胞更高水平的平滑肌肌球蛋白重链（平滑肌细胞分化的标志物）表达。与对增殖和收缩蛋白表达的影响相反，FN和LM都支持PDGF引起的细胞迁移。此外，FN和LM都支持响应PDGF和bFGF的ERK 1和ERK 2的激活。然而，FN和LM在通过粘着斑激酶（FAK）支持信号传导的能力上确实存在差异。在FN上培养的PCASMC显示出响应于PDGF或bFGF的FAK的强烈活化，然而，在LM上培养的细胞显示出响应于生长因子的FAK的几乎没有活化。结果表明，整合素信号通路对VSMC的增殖和表型有着重要的影响，而FAB是这些信号通路的重要中间体。我们的研究结果的影响的机制控制VSMC增殖和表型的病理状态，如动脉粥样硬化和再狭窄进行了讨论。(C)北京大学出版社.
Extracellular matrix proteins such as fibronectin (FN) and laminin (LM) are known to help control the growth and phenotype of vascular smooth muscle cells (VSMCs). Here we have analyzed the relationship between growth factor and integrin signaling pathways in VSMCs. Culturing porcine coronary artery smooth muscle cells (PCASMCs) on FN and LM leads to distinct effects on cell proliferation and contractile protein expression. PCASMCs cultured on FN proliferate at a higher rate than cells cultured on LM, regardless of the growth factor used to support proliferation. Moreover, cells cultured on LM show higher levels of expression of smooth muscle myosin heavy chain (a marker of smooth muscle cell differentiation) than cells cultured on FN. In contrast to the effects on proliferation and contractile protein expression, both FN and LM supported cell migration in response to PDGF. Also, both FN and LM supported activation of ERK1 and ERK2 in response to PDGF and bFGF. However, FN and LM did show a difference in their ability to support signaling through the focal adhesion kinase (FAK). PCASMCs cultured on FN show robust activation of FAK in response to either PDGF or bFGF, however, cells cultured on LM show little-to-no activation of FAK in response to the growth factors. The results show that integrin signaling pathways have a profound effect on VSMC proliferation and phenotype, and that FAB is an important intermediate in these signaling pathways. The implications of our findings on the mechanisms controlling VSMC proliferation and phenotype in pathological states such as atherosclerosis and restenosis are discussed. (C) 2000 Academic Press.