...
首页> 外文期刊>Endocrinology >Glucose-oxidized low-density lipoproteins enhance insulin-like growth factor I-stimulated smooth muscle cell proliferation by inhibiting integrin-associated protein cleavage.
【24h】

Glucose-oxidized low-density lipoproteins enhance insulin-like growth factor I-stimulated smooth muscle cell proliferation by inhibiting integrin-associated protein cleavage.

机译:葡萄糖氧化的低密度脂蛋白通过抑制整合素相关的蛋白裂解,增强了胰岛素样生长因子I刺激的平滑肌细胞增殖。

获取原文
获取原文并翻译 | 示例
           

摘要

Prior published reports have demonstrated that glucose-oxidized low-density lipoproteins (g-OxLDL) enhance the proliferative response of vascular smooth muscle cells (SMC) to IGF-I. Our previous studies have determined that the regulation of cleavage of integrin-associated protein (IAP) by matrix-metalloprotease-2 (MMP-2) in diabetic mice in response to hyperglycemia is a key regulator of the response of SMC to IGF-I. Because chronic hyperglycemia enhances glucose-induced LDL oxidation, these studies were conducted to determine whether g-OxLDL modulates the response of SMC to IGF-I by regulating MMP-2-mediated cleavage of IAP. We determined that exposure of SMC to g-OxLDL, but not native LDL, was sufficient to facilitate an increase in cell proliferation in response to IGF-I. Exposure to an anti-CD36 antibody, which has been shown to inhibit g-OxLDL-mediated signaling, inhibited the effects of g-OxLDL on IGF-I-stimulated SMC proliferation. The effect of g-OxLDL could be attributed, in part, to an associated decrease in proteolytic cleavage of IAP leading to increase in the basal association between IAP and Src homology 2 domain-containing protein tyrosine phosphatase substrate-1, which is required for IGF-I-stimulated proliferation. The inhibitory effect of g-OxLDL on IAP cleavage appeared to be due to its ability to decrease the amount of activated MMP-2, the protease responsible for IAP cleavage. In conclusion, these data provide a molecular mechanism to explain previous studies that have reported an enhancing effect of g-OxLDL on IGF-I-stimulated SMC proliferation.
机译:先前已发表的报告已经证明,葡萄糖氧化的低密度脂蛋白(g-OxLDL)增强了血管平滑肌细胞(SMC)对IGF-1的增殖反应。我们以前的研究已经确定,糖尿病小鼠对高血糖的反应中基质金属蛋白酶2(MMP-2)对整联蛋白相关蛋白(IAP)的裂解调控是SMC对IGF-I反应的关键调节因子。由于慢性高血糖症会增强葡萄糖诱导的LDL氧化,因此进行了这些研究,以确定g-OxLDL是否通过调节MMP-2介导的IAP裂解来调节SMC对IGF-I的反应。我们确定SMC暴露于g-OxLDL而不是天然LDL足以促进细胞对IGF-1的增殖。暴露于抗CD36抗体(已显示可抑制g-OxLDL介导的信号传导)可抑制g-OxLDL对IGF-I刺激的SMC增殖的影响。 g-OxLDL的作用可能部分归因于IAP的蛋白水解切割的相关减少,导致IAP和IGF所需的含Src同源性2结构域的蛋白酪氨酸磷酸酶底物1之间的基础缔合增加。 -我刺激了增殖。 g-OxLDL对IAP裂解的抑制作用似乎是由于其减少了活化IMP裂解的蛋白酶MMP-2的能力。总之,这些数据提供了解释先前研究的分子机制,这些研究报告了g-OxLDL对IGF-I刺激的SMC增殖的增强作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号