Insulin-like growth factor-II regulates the expression of vascular endothelial growth factor by the human keratinocyte cell line HaCaT
Insulin-like growth factor-II regulates the expression of vascular endothelial growth factor by the human keratinocyte cell line HaCaT
复制标题
DOI：
10.1111/j.0022-202x.2004.22735.x
复制
发表时间：
2004-07-01
影响因子：
6.5
通讯作者：
Kim, KW
中科院分区：
文献类型：
--
作者：
Kwon, YW;Kwon, KS;Kim, KW
银屑病是一种慢性复发性皮肤病，其特征在于血管生成增强。导致血管过多的发病机制有待进一步研究。据报道，一种有效的血管生成因子，血管内皮生长因子（VEGF）在银屑病表皮中过表达，并且胰岛素样生长因子II（IGF-II）的水平在银屑病病变的组织液和血清中显著升高。我们认为IGF-II可能作为VEGF的旁分泌诱导剂发挥作用。在这里，我们证明了HaCaT角质形成细胞暴露于IGF-II通过MAP激酶（细胞外信号调节激酶（ERK 2）途径诱导VEGF的mRNA和蛋白表达。特别地，我们确定了ERK 2的磷酸化而不是p38和JNK 1/2的磷酸化被IGF-II以时间依赖性的方式激活。此外，我们发现IGF-II处理通过MAP激酶途径诱导MDM 2的表达。此外，MDM 2的增加导致p53水平降低，随后HIF-1 α和VEGF表达增加。总之，这些结果表明，IGF-II通过增加HIF-1 α水平增强HaCaT细胞中VEGF的表达。
Psoriasis is a chronic, relapsing skin disease characterized by enhanced angiogenesis. The pathogenetic process resulting in hypervascularity remains to be further investigated. It has been reported that a potent angiogenic factor, vascular endothelial growth factor (VEGF) is overexpressed in psoriatic epidermis and that the level of insulin-like growth factor II (IGF-II) is significantly elevated in the tissue fluid and serum of the psoriatic lesion. We considered the possibility that IGF-II might function as a paracrine inducer of VEGF. Here, we demonstrated that exposure of HaCaT keratinocytes to IGF-II induced both mRNA and protein expression of VEGF through the MAP kinase (extracellular signal-regulated kinase (ERK2) pathway. Particularly, we determined that phosphorylation of ERK2 but not p38 and JNK1/2 was activated by IGF-II in a time-dependent manner. Additionally, we found that IGF-II treatment induced the expression of MDM2 through the MAP kinase pathway. Moreover, the increase of MDM2 resulted in decreased levels of p53 followed by increased expression of HIF-1alpha and VEGF. Taken together, these results suggest that IGF-II enhances the expression of VEGF in HaCaT cells by increasing HIF-1alpha levels.