Role of the integrin αVβ3 in mediating increased smooth muscle cell responsiveness to IGF-I in response to hyperglycemic stress

作者: David R. Clemmons , Laura A. Maile , Yan Ling , J. Yarber , Walker H. Busby

DOI: 10.1016/J.GHIR.2007.01.004

关键词:

摘要: Under usual conditions, the role of IGF-I in vascular cell types is to maintain cellular protein synthesis and size, even excess does not stimulate proliferation. In pathophysiologic states, such as hyperglycemia, smooth muscle cells (SMC) de-differentiate change their responsiveness IGF-I. During hyperglycemia stimulates both SMC migration Our laboratory has investigated molecular mechanism by which this mediated. Following secrete increased concentrations thrombospondin, vitronectin osteopontin, ligands for integrin αVβ3. Activation αVβ3 recruitment a tyrosine phosphatase, SHP-2. Exposure results phosphorylation transmembrane protein, SHPS-1, provides docking site αVβ3-associated After stimulation SHP-2 associates with Src kinase, signaling Shc. phosphorylates Shc, resulting activation MAP kinases, are necessary proliferation migration. Blocking an inability Shc phosphorylation. conditions normoglycemia, there insufficient recruit SHP-2, no increase can be demonstrated SMC. contrast, if added normal glucose, events that reconstituted. Therefore when exposed glucose they protected from excessive mitogenesis With marked response sustained. These findings indicate hyperglycemic stress may leads altered signaling, allows undergo mitogenic response, contribute development atherosclerosis.

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