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p38 Mitogen-activated protein kinase mediates hypoxia-induced vascular endothelial growth factor release in human endothelial cells

Fan Bei, Wang Yanxia, Yao Tai, Zhu Yichun

Department of Physiology and Pathophysiology, Key Laboratory of Molecular Medicine of The Ministry of Education, Fudan University Shanghai Medical College.Shanghai 200032

Abstract

Increased vascular endothelial growth factor (VEGF) biosynthesis in vascular endothelial cells has been reported to play an obligatory role in promoting angiogenesis. Nevertheless, the intracellular signaling mechanisms of hypoxia-induced VEGF release remain largely unknown. Human umbilical vein endothelial cell lines (ECV304) were cultured in normoxic or hypoxic conditions for 12-24 hours and harvested for determination of VEGF mRNA expression and phosphorylation of ERK1/2 and p38 MAPK by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. Secreted VEGF protein was measured by enzyme-linked immunosorbent assay (ELISA). It has reported that PD98059, an ERK inhibitor, was able to blunt the hypoxia-induced activation of the expression of VEGF gene. In accordance with this report, an increase in ERK1/2 phosphorylation and VEGF biosynthesis was observed in ECV304 cells cultured in hypoxia, and this increase was blocked by PD98059. The novel finding of the present study is that an activation of p38 MAP kinase is involved in hypoxia-induced increase in VEGF biosynthesis. SB202190, an inhibitor of p38 MAPK was able to blunt the hypoxia-induced increase in VEGF biosynthesis. These dada provide the first direct evidence for a role of p38 MAPK in mediating hypoxia-induced increase in VEGF biosynthesis in human endothelial cells.

Key words: Hypoxia;Vascular endothelial growth factor;Vascular endothelial cells;Mitogen-activated protein kinase p38;Signal transduction

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Citing This Article：

Fan Bei, Wang Yanxia, Yao Tai, Zhu Yichun. p38 Mitogen-activated protein kinase mediates hypoxia-induced vascular endothelial growth factor release in human endothelial cells. Acta Physiol Sin 2005; 57 (1): (in Chinese with English abstract).