Enhanced proliferation and migration of vascular smooth muscle cells in response to vascular injury under hyperglycemic conditions is controlled by beta3 integrin signaling.
Enhanced proliferation and migration of vascular smooth muscle cells in response to vascular injury under hyperglycemic conditions is controlled by beta3 integrin signaling.
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DOI：
10.1016/j.biocel.2010.02.009
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发表时间：
2010-06
影响因子：
4
通讯作者：
Smyth, Susan S.
中科院分区：
文献类型：
--
作者：
Panchatcharam, Manikandan;Miriyala, Sumitra;Yang, Fanmuyi;Leitges, Michael;Chrzanowska-Wodnicka, Magdalena;Quilliam, Lawrence A.;Anaya, Paul;Morris, Andrew J.;Smyth, Susan S.
经皮血管介入治疗后动脉粥样硬化的形成和再狭窄涉及血管平滑肌细胞(SMCs)的生长和迁移到新的内膜病变中，部分原因是细胞外基质的变化。虽然一些临床研究表明，与非糖尿病患者相比，糖尿病患者的β3整合素抑制可防止再狭窄，但对β3整合素抑制在这方面的作用知之甚少。为了了解整合素介导的糖尿病小鼠系膜细胞功能调节的分子机制，我们检测了整合素β3缺陷的糖尿病小鼠的系膜细胞反应，观察到整合素是促进增殖、迁移和细胞外调节激酶激活所必需的。高血糖以整合素β3依赖的方式增强PKCβ的膜募集和催化活性。高血糖还可促进系膜细胞丝状足突的形成和细胞迁移，这两个过程都需要αVβ3、蛋白激酶Cβ和ERK活性。此外，在高血糖条件下，αVβ3整合素配体凝血酶敏感蛋白和整合素调节剂RAP1调节整合素-激酶的结合。这些结果表明，血管平滑肌细胞对血管损伤的反应因是否存在高血糖而有所不同，高血糖条件下的平滑肌细胞反应主要是通过β3整合素信号介导的
Atheroma formation and restenosis following percutaneous vascular intervention involve the growth and migration of vascular smooth muscle cells (SMCs) into neointimal lesions, in part due to changes in the extracellular matrix. While some clinical studies have suggested that, in comparison to non-diabetics, β3 integrin inhibition in diabetic patients confers protection from restenosis, little is known regarding the role of β3 integrin inhibition on SMC responses in this context. To understand the molecular mechanisms underlying integrin-mediated regulation of SMC function in diabetes, we examined SMC responses in diabetic mice deficient in integrin β3 and observed that the integrin was required for enhanced proliferation, migration and extracellular regulated kinase (ERK) activation. Hyperglycemia enhanced membrane recruitment and catalytic activity of PKCβ in an integrin β3-dependent manner. Hyperglycemia also promoted SMC filopodia formation and cell migration, both of which required αVβ3, PKCβ, and ERK activity. Furthermore, the integrin–kinase association was regulated by the αVβ3 integrin ligand thrombospondin and the integrin modulator Rap1 under conditions of hyperglycemia. These results suggest that there are differences in SMC responses to vascular injury depending on the presence or absence of hyperglycemia and that SMC response under hyperglycemic conditions is largely mediated through β3 integrin signaling
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