Rho-kinase and myosin II activities are required for cell type and environment specific migration
Rho-kinase and myosin II activities are required for cell type and environment specific migration
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DOI：
10.1111/j.1365-2443.2005.00823.x
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发表时间：
2005-02-01
期刊：
影响因子：
2.1
通讯作者：
Kaibuchi, K
中科院分区：
文献类型：
--
作者：
Nakayama, M;Amano, M;Kaibuchi, K
细胞迁移在动脉粥样硬化病变的发展中很重要。巨噬细胞和平滑肌细胞迁移到动脉内皮下间隙，导致斑块形成。长期抑制 Rho 激酶活性可诱导动脉粥样硬化性冠状动脉病变消退，这可能是通过阻止巨噬细胞和平滑肌细胞的迁移来实现的。然而，之前有关 Rho 激酶抑制剂对细胞迁移影响的报道是相互矛盾的。我们在这里检查了 Rho 激酶抑制剂的细胞类型特异性，发现在三维迁移测定中，内皮细胞、巨噬细胞和平滑肌细胞的迁移受到 Rho 激酶抑制剂处理的剂量依赖性抑制，而成纤维细胞和上皮细胞的迁移则没有受到抑制。肌球蛋白 II 抑制剂以类似于 Rho 激酶抑制剂的方式阻止细胞迁移。相比之下，在二维迁移测定中，对于所检查的任何细胞类型，Rho 激酶或肌球蛋白 II 抑制剂均不会抑制细胞迁移。综上所述，这些结果表明 Rho 激酶抑制剂通过调节肌球蛋白 II 活性来抑制特定条件下特定细胞类型的迁移。我们的研究结果表明，Rho激酶是伴有白细胞和平滑肌细胞侵袭的动脉粥样硬化的治疗靶点。
Cell migration is important in the development of atherosclerotic lesions. Macrophages and smooth muscle cells migrate into the subendothelial space of arteries, leading to plaque formation. Long-term inhibition of the activity of Rho-kinase induces a regression of atherosclerotic coronary lesions, probably by preventing migration of macrophages and smooth muscle cells. Previous reports concerning the effect of Rho-kinase inhibitors on cell migration are contradictory, however. We examined here the cell type specificity of Rho-kinase inhibitors and found that migration of endothelial cells, macrophages, and smooth muscle cells was inhibited by treatment with Rho-kinase inhibitors in a dose-dependent fashion in a three-dimensional migration assay, whereas that of fibroblasts and epithelial cells was not inhibited. Myosin II inhibitor prevented cell migration in a manner similar to Rho-kinase inhibitors. In contrast, in a two-dimensional migration assay, cell migration was not inhibited by Rho-kinase or myosin II inhibitors for any of the cell types examined. Taken together, these results indicate that Rho-kinase inhibitors suppress migration of specific cell types under specific conditions through the regulation of myosin II activity. Our findings suggest that Rho-kinase is the therapeutic target of atherosclerosis accompanied with invasion by leukocytes and smooth muscle cells.