Department of Vascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China.
Mol Cells. 2013 Aug;36(2):112-8. doi: 10.1007/s10059-013-0012-2. Epub 2013 Jun 25.
The migration and proliferation of vascular smooth muscle cells (VSMCs) are essential elements during the development of atherosclerosis and restenosis. An increasing number of studies have reported that extracellular matrix (ECM) proteins, including the CCN protein family, play a significant role in VSMC migration and proliferation. CCN4 is a member of the CCN protein family, which controls cell development and survival in multiple systems of the body. Here, we sought to determine whether CCN4 is involved in VSMC migration and proliferation. We examined the effect of CCN4 using rat cultured VSMCs. In cultured VSMCs, CCN4 stimulated the adhesion and migration of VSMCs in a dose-dependent manner, and this effect was blocked by an antibody for integrin α5β1. CCN4 expression was enhanced by the pro-inflammatory cytokine tumor necrosis factor α (TNF-α). Furthermore, knockdown of CCN4 by siRNA significantly inhibited the VSMC proliferation. CCN4 also could up-regulate the expression level of marker proteins of the VSMCs phenotype. Taken together, these results suggest that CCN4 is involved in the migration and proliferation of VSMCs. Inhibition of CCN4 may provide a promising strategy for the prevention of restenosis after vascular interventions.
血管平滑肌细胞（VSMCs）的迁移和增殖是动脉粥样硬化和再狭窄发展过程中的重要因素。越来越多的研究表明，细胞外基质（ECM）蛋白，包括 CCN 蛋白家族，在 VSMC 迁移和增殖中发挥重要作用。CCN4 是 CCN 蛋白家族的一员，它在体内多个系统中控制着细胞的发育和存活。在这里，我们试图确定 CCN4 是否参与了 VSMC 的迁移和增殖。我们使用大鼠培养的 VSMCs 来研究 CCN4 的作用。在培养的 VSMCs 中，CCN4 以剂量依赖的方式刺激 VSMCs 的黏附和迁移，而这种作用被整合素 α5β1 的抗体所阻断。促炎细胞因子肿瘤坏死因子 α（TNF-α）可增强 CCN4 的表达。此外，siRNA 下调 CCN4 可显著抑制 VSMC 的增殖。CCN4 还可以上调 VSMC 表型标志物的表达水平。综上所述，这些结果表明 CCN4 参与了 VSMCs 的迁移和增殖。抑制 CCN4 可能为预防血管介入后的再狭窄提供一种有前途的策略。
