Adiponectin inhibits insulin-like growth factor-1-induced cell migration by the suppression of extracellular signal-regulated kinase 1/2 activation, but not Akt in vascular smooth muscle cells
Adiponectin inhibits insulin-like growth factor-1-induced cell migration by the suppression of extracellular signal-regulated kinase 1/2 activation, but not Akt in vascular smooth muscle cells
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DOI：
10.1038/hr.2008.19
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发表时间：
2009-03-01
影响因子：
5.4
通讯作者：
Tamaki, Toshiaki
中科院分区：
文献类型：
--
作者：
Motobayashi, Yuki;Izawa-Ishizawa, Yuki;Tamaki, Toshiaki
脂联素是一种脂肪细胞来源的激素，已被认为通过抑制多种生长因子而显示出抗动脉粥样硬化的特性。胰岛素样生长因子-1（IGF-1）是一种强有力的有丝分裂原，在动脉粥样硬化的发生和斑块稳定中起重要作用。本研究的目的是阐明脂联素对IGF-1诱导的血管平滑肌细胞（VSMCs）迁移及其细胞内信号通路的影响。在这项研究中，我们评估了细胞迁移和几个激酶活性培养大鼠主动脉平滑肌细胞（RASMCs）。脂联素预处理抑制IGF-1诱导的细胞迁移和细胞外信号调节激酶（ERK）1/2的激活，ERK 1/2是IGF-1诱导的细胞迁移的主要介质之一。在RASMC中，脂联素和5-氨基咪唑-4-甲酰胺核苷（AICAR），一种5 '-AMP激活的蛋白激酶（AMPK）激活剂，刺激AMPK激活。AICAR激活AMPK可抑制IGF-1诱导的RASMCs ERK 1/2激活和细胞迁移。另一方面，Akt和Bad的磷酸化，Bcl-2家族的促凋亡分子，这是增加IGF-1的刺激，并没有减少与脂联素的预处理。结果表明，脂联素通过抑制ERK 1/2的活化而抑制IGF-1诱导的VSMC迁移，这可能与AMPK的活化有关。此外，脂联素选择性抑制ERK 1/2途径，而不是Akt-Bad途径，由IGF-1刺激。从这些发现，这意味着脂联素抑制IGF-1诱导的VSMC迁移及其信号选择性。
Adiponectin, an adipocyte-derived hormone, has been proposed to show antiatherogenic properties through the inhibitory effects against various growth factors. Insulin-like growth factor-1 (IGF-1) is one of the potent mitogens, which has been considered to play important roles in both atherogenesis and plaque stabilization in accordance to the phase of atherosclerosis. The aim of this study is to elucidate the adiponectin effects on IGF-1-induced cell migration and its intracellular signaling pathways in vascular smooth muscle cells (VSMCs). In this study, we assessed cell migration and several kinase activities in cultured rat aortic smooth muscle cells (RASMCs). Adiponectin pretreatment suppressed IGF-1-induced cell migration and extracellular signal-regulated kinase (ERK) 1/2 activation, which is one of the major mediators for IGF-1-induced cell migration. In RASMCs, adiponectin and 5-aminoimidazole-4-carboxamide riboside (AICAR), a 5'-AMP-activated protein kinase (AMPK) activator, stimulated AMPK activation. AMPK activation by AICAR inhibited IGF-1-induced ERK1/2 activation and cell migration in RASMCs. On the other hand, phosphorylation of Akt and Bad, proapoptotic molecules of the Bcl-2 family, which were increased by IGF-1 stimulation, was not diminished by the pretreatment with adiponectin. It was shown that adiponectin inhibited IGF-1-induced VSMC migration through suppression of ERK1/2 activation, which might be implicated in AMPK activation. Furthermore, adiponectin selectively inhibited ERK1/2 pathway, not Akt-Bad pathway, stimulated by IGF-1. From these findings, it was implied that adiponectin suppressed IGF-1-induced VSMC migration and its signaling selectivity.