STRIP2 silencing inhibits vascular smooth muscle cell proliferation and migration via P38-AKT-MMP-2 signaling pathway
STRIP2 silencing inhibits vascular smooth muscle cell proliferation and migration via P38-AKT-MMP-2 signaling pathway
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DOI：
10.1002/jcp.28810
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发表时间：
2019-12-01
影响因子：
5.6
通讯作者：
Li, Shengnan
中科院分区：
文献类型：
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作者：
Dai, Li;Zhou, Jun;Li, Shengnan
据报道，STRIP2 （FAM40B）调控肿瘤细胞迁移。我们的研究旨在探讨STRIP2在小鼠主动脉平滑肌细胞（aortic smooth muscle cell， MOVAS）增殖和迁移过程中的作用，而MOVAS在动脉粥样硬化形成中起着重要作用。在MOVAS细胞中，STRIP2缺失抑制了细胞的增殖和迁移，这与基质金属蛋白酶-2 (MMP-2)/MMP-9的表达显著降低有关。此外，p38丝裂原激活的蛋白激酶和蛋白激酶B （AKT）失活，而细胞外信号调节激酶（ERK1/2）和jun n-末端激酶（JNK）在STRIP2沉默时被激活。SB203580 （P38抑制剂）进一步降低AKT磷酸化（p-AKT），而脱氢紫碱氯（Dc； P38激活剂）逆转了这一作用。此外，Dc显著恢复了strip2敲除细胞中MMP-2的表达。正如预期的那样，过表达STRIP2表现出相反的效果。Dc和AKT激活剂SC79逆转了STRIP2沉默诱导的细胞增殖和迁移抑制。有趣的是，STRIP2缺失显著提高了血管内皮生长因子水平。综上所述，STRIP2通过P38-AKT-MMP-2信号传导在MOVAS细胞中促进细胞增殖和迁移，表明STRIP2在动脉粥样硬化中的重要性。
STRIP2 (FAM40B) was reported to regulate tumor cell migration. Our study aims to discuss the effect of STRIP2 in mouse aortic smooth muscle cell (MOVAS) proliferation and migration processes, which contributes greatly to atherosclerosis formation. In MOVAS cells, STRIP2 depletion suppressed cell proliferation and migration, which were related to a remarkable decrease in matrix metalloproteinases-2 (MMP-2)/MMP-9 expression. Additionally, P38mitogen-activated protein kinases and Protein kinase B (AKT) are inactivated while extracellular signal-regulated kinase (ERK1/2) and jun N-terminal kinase (JNK) are activated upon STRIP2 silencing. SB203580 (P38 inhibitor) further reduced AKT phosphorylation (p-AKT) while dehydrocorydaline chloride (Dc; P38 activator) reversed this effect. Furthermore, Dc significantly recovered MMP-2 expression in STRIP2-knockdown cells. As expected, overexpressing STRIP2 exhibited a contrary effect. Dc and AKT activator SC79 reversed the inhibition of cell proliferation and migration induced by STRIP2 silencing. Interestingly, STRIP2 depletion increased vascular endothelial growth factor level significantly. Taken together, STRIP2 contributed to cell proliferation and migration through P38-AKT-MMP-2 signaling in MOVAS cells, indicating the importance of STRIP2 in atherosclerosis.