Nesfatin-1 promotes VSMC migration and neointimal hyperplasia by upregulating matrix metalloproteinases and downregulating PPAR gamma
Nesfatin-1 promotes VSMC migration and neointimal hyperplasia by upregulating matrix metalloproteinases and downregulating PPAR gamma
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Nesfatin-1通过上调基质金属蛋白酶和下调PPARγ促进VSMC迁移和新生内膜增生
DOI：
10.1016/j.biopha.2018.03.120
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发表时间：
2018
影响因子：
7.5
通讯作者：
Sun Hai Jian
中科院分区：
文献类型：
--
作者：
Zhang Ji Ru;Lu Qing Bo;Feng Wu Bing;Wang Hui Ping;Tang Zi Han;Cheng Han;Du Qiong;Wang Yuan Ben;Li Ke Xue;Sun Hai Jian
血管平滑肌细胞(VSMCs)的去分化、增殖和迁移在高血压、动脉粥样硬化和内膜增生的发生发展过程中起着至关重要的作用。Nesfatin-1是一种潜在的心血管功能调节剂。然而，Nesfatin-1在VSMC生物学中的作用尚不清楚。本研究旨在探讨Nesfatin-1在血管损伤后VSMC增殖、迁移和内膜增生中的调节作用。在此，我们证明了Nesfatin-1在体外促进VSMC表型从收缩状态向合成状态转变，刺激VSMC的增殖和迁移。在分子水平上，Nesfatin-1上调VSMC的蛋白和基因水平，上调基质金属蛋白酶2和MMP9的启动子活性，但下调过氧化物酶体增殖物激活受体γ(PPARγ)水平和启动子活性。阻断MMP2/9或激活PPARγ可阻止Nesfatin-1诱导的VSMC的增殖和迁移。在体内，Nesfatin-1抑制大鼠颈动脉损伤后新生内膜的形成。综上所述，我们的结果表明，Nesfatin-1通过上调MMP2/MMP9的水平和抑制PPARγ的表达来促进血管平滑肌细胞的增殖、迁移和新生内膜的增殖。
The dedifferentiation, proliferation and migration of vascular smooth muscle cells (VSMCs) are essential in the progression of hypertension, atherosclerosis and intimal hyperplasia. Nesfatin-1 is a potential modulator in cardiovascular functions. However, the role of nesfatin-1 in VSMC biology has not been explored. The present study was designed to determine the regulatory role of nesfatin-1 in VSMC proliferation, migration and intimal hyperplasia after vascular injury. Herein, we demonstrated that nesfatin-1 promoted VSMC phenotype switch from a contractile to a synthetic state, stimulated VSMC proliferation and migrationin vitro. At the molecular level, nesfatin-1 upregulated the protein and mRNA levels, as well as the promoter activities of matrix metalloproteinase 2 (MMP-2) and MMP-9, but downregulated peroxisome proliferator-activated receptor γ (PPARγ) levels and promoter activity in VSMCs. Blockade of MMP-2/9 or activation of PPARγ prevented the nesfatin-1-induced VSMC proliferation and migration.In vivo, knockdown of nesfatin-1 ameliorated neointima formation following rat carotid injury. Taken together, our results indicated that nesfatin-1 stimulated VSMC proliferation, migration and neointimal hyperplasia by elevating MMP2/MMP-9 levels and inhibiting PPARγ gene expression.