ERK5 MAPK regulates embryonic angiogenesis and acts as a hypoxia-sensitive repressor of vascular endothelial growth factor expression
ERK5 MAPK regulates embryonic angiogenesis and acts as a hypoxia-sensitive repressor of vascular endothelial growth factor expression
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DOI：
10.1074/jbc.m207573200
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发表时间：
2002-11-08
影响因子：
4.8
通讯作者：
Winoto, A
中科院分区：
文献类型：
--
作者：
Sohn, SJ;Sarvis, BK;Winoto, A
在血管生成过程中，内皮细胞经历增殖、重组和稳定以建立成熟的血管网络。这一过程对于发育过程中建立功能性循环系统至关重要，并有助于肿瘤生长的病理过程。在此，我们报告 ERK5 MAPK 缺陷的胚胎在胚胎第 10.5 天至 11.5 天之间死亡，并伴有血管生成衰竭和心血管缺陷。我们发现 ERK5 缺陷会导致血管内皮生长因子 (VEGF) 表达增加，其失调已被证明会阻碍血管生成重塑和血管稳定。我们的数据还表明，ERK5 在缺氧反应期间负向调节 vegf 基因座的转录。重要的是，ERK5 在比 p38a 更早的发育阶段是必需的，而 p38a 不能弥补 ERK5 的缺陷。这些结果表明ERK5在早期血管生成的调节中发挥特定作用。
During angiogenesis, endothelial cells undergo proliferation, reorganization, and stabilization to establish a mature vascular network. This process is critical for establishing a functional circulatory system during development and contributes to the pathological process of tumor growth. Here we report that embryos deficient for the ERK5 MAPK die between embryonic days 10.5 and 11.5 with angiogenic failure and cardiovascular defects. We show that ERK5 deficiency leads to an increased expression of the vascular endothelial growth factor (VEGF), dysregulation of which has been shown to impede angiogenic remodeling and vascular stabilization. Our data also reveal that ERK5 negatively regulates transcription from the vegf locus during hypoxic responses. Importantly, ERK5 is required at an earlier developmental stage than p38a, and p38a does not compensate for ERK5 deficiency. These results demonstrate that ERK5 plays a specific role in the regulation of early angiogenesis.