Stabilization of vascular endothelial growth factor mRNA by hypoxia-inducible factor 1

被引：197

作者：

Liu, LX ^{[1
]}

Lu, HW ^{[1
]}

Luo, YX ^{[1
]}

Date, T ^{[1
]}

Belanger, AJ ^{[1
]}

Vincent, KA ^{[1
]}

Akita, GY ^{[1
]}

Goldberg, M ^{[1
]}

Cheng, SH ^{[1
]}

Gregory, RJ ^{[1
]}

Jiang, CW ^{[1
]}

机构：

[1] Genzyme Corp, Framingham, MA 01701 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2002年 / 291卷 / 04期

关键词：

HIF; vascular endothelial growth factor; hypoxia; mRNA stability;

D O I：

10.1006/bbrc.2002.6551

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Hypoxia regulates expression of vascular endothelial growth factor (VEGF) by increasing its transcription and by stabilizing its mRNA. Despite the pivotal role of hypoxia-inducible factor 1 (HIF-1) in transcriptional activation of hypoxia-responsive genes, it is not known whether HIF-1 mediates hypoxia-induced stabilization of VEGF mRNA. We constructed adenoviral vectors expressing either the wild-type HIF-1alpha (Ad2/HIF-1alpha/FL), a constitutively stable hybrid form of HIF-1alpha (Ad2/HIF-1alpha/VP16), or no transgene (Ad2/CMVEV). In rat glioma (C6) cells and human cardiac, vascular smooth muscle, and endothelial cells, infection with Ad2/HIF-1alpha/VP16 or Ad2/HIF-1alpha/FL increased VEGF expression at both the mRNA and protein levels. Under normoxic conditions, the half-life of VEGF mRNA was 42 min in C6 cells. Hypoxia and Ad2/HIF-1alpha/VP16 increased the half-life of VEGF mRNA to 3.3 and 2.7 h, respectively, while Ad2/CMVEV had no effect. These studies are the first to demonstrate that overexpression of HIP-la increases VEGF mRNA stability. Our results also suggest that stabilization of VEGF mRNA by hypoxia is mediated, at least in part, by HIF-1. (C) 2002 Elsevier Science (USA).

引用

页码：908 / 914

页数：7

共 46 条

[21] Activation of HIF1α ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex [J].