Fujita Nobuya, Furukawa Yusuke, Du Jian, Itabashi Naoki, Fujisawa Genro, Okada Koji, Saito Toshikazu, Ishibashi Shun
Department of Medicine, Division of Endocrinology and Metabolism, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, 329-0498, Tochigi, Japan.
Mol Cell Endocrinol. 2002 Jun 28;192(1-2):75-84. doi: 10.1016/s0303-7207(02)00108-9.
To clarify the mechanisms of hyperglycemia-induced proliferation of vascular smooth muscle cells (VSMC), we examined the effects of high glucose (HG) on nuclear factor (NF)-kappaB and E2F-1. Angiotensin II (Ang II) significantly enhanced DNA binding activity of NF-kappaB under HG (25.6 mM) conditions with an increase in p65 subunit of NF-kappaB, and did it slightly under normal glucose (NG; 5.6 mM) conditions. Ang II failed to induce E2F-1 expression, or its binding to the cdc2 promoter, even under HG conditions. HG greatly augmented the cdc2 inducibility of fetal calf serum (FCS), through the increase in E2F-1 activity. These data indicate that hyperglycemia contributes to abnormal proliferation of VSMC by two mechanisms; the induction of NF-kappaB activation by Ang II, which facilitates transcription of certain growth factors, and the augmentation of E2F-1 in response to growth factors.
为了阐明高血糖诱导血管平滑肌细胞（VSMC）增殖的机制，我们研究了高糖（HG）对核因子（NF）-κB和E2F-1的影响。在HG（25.6 mM）条件下，血管紧张素II（Ang II）显著增强了NF-κB的DNA结合活性，同时NF-κB的p65亚基增加，而在正常葡萄糖（NG；5.6 mM）条件下作用轻微。即使在HG条件下，Ang II也未能诱导E2F-1表达或其与cdc2启动子的结合。HG通过增加E2F-1活性，极大地增强了胎牛血清（FCS）对cdc2的诱导能力。这些数据表明，高血糖通过两种机制导致VSMC异常增殖：Ang II诱导NF-κB激活，促进某些生长因子的转录；以及对生长因子作出反应时E2F-1增加。
