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TIPE2 deficiency accelerates neointima formation by downregulating smooth muscle cell differentiation

机译:TIPE2缺乏症通过下调平滑肌细胞分化来加速新内膜形成

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Phenotypic switching of vascular smooth muscle cells (VSMCs) is known to play a key role in the development of atherosclerosis. However, the mechanisms that mediate VSMC phenotypic switching are unclear. We report here that TIPE 2, the tumor necrosis factor (TNF) ??-induced protein 8-like 2 (TNFAIP8L2), plays an atheroprotective role by regulating phenotypic switching of VSMCs in response to oxidized low-density lipoprotein (ox-LDL) stimuli. TIPE 2-deficient VSMCs treated with ox-LDL expressed lower levels of contractile proteins such as SMaA, SM-MHC and calponin, whereas the proliferation, migration and the synthetic capacity for growth factors and cytokines were increased remarkably. Furthermore, TIPE 2 inhibited VSMCs proliferation by preventing G1/S phase transition. Interestingly, these effects of TIPE 2 on VSMCs were dependent on P38 and ERK1/2 kinase signals. As a result, neointima formation was accelerated in the carotid arteries of TIPE 2-deficient mice. These results indicate that TIPE 2 is a potential inhibitor of atherosclerosis. ? 2013 Landes Bioscience.
机译:血管平滑肌细胞(VSMC)的表型转换在动脉粥样硬化的发展中起着关键作用。但是,介导VSMC表型转换的机制尚不清楚。我们在这里报告TIPE 2,肿瘤坏死因子(TNF)??诱导蛋白8样2(TNFAIP8L2),通过调节VSMC响应氧化型低密度脂蛋白(ox-LDL)的表型转换,起到了动脉粥样硬化的保护作用。刺激。用ox-LDL处理的TIPE 2缺陷型VSMC表达的收缩蛋白水平较低,例如SMaA,SM-MHC和钙蛋白,而生长因子和细胞因子的增殖,迁移和合成能力显着增加。此外,TIPE 2通过阻止G1 / S相转变来抑制VSMC增殖。有趣的是,TIPE 2对VSMC的这些作用取决于P38和ERK1 / 2激酶信号。结果,在TIPE 2缺陷小鼠的颈动脉中新内膜形成加速。这些结果表明TIPE 2是潜在的动脉粥样硬化抑制剂。 ? 2013 Landes生物科学。

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