Department of Food and Nutrition, Chung-Ang University, Anseong 456-756, Korea.
School of Korean Medicine and Healthy Aging Korean Medicine Research Center, Pusan National University, Yangsan, 626-780, Republic of Korea.
Sci Rep. 2017 Mar 20;7:44687. doi: 10.1038/srep44687.
We report a pivotal role for IL-5 as an angiogenic activator. IL-5 increased proliferation, migration and colony tube formation in HUVECs associated with the phosphorylation of ERK and AKT/eNOS, and promoted microvessel sprouting from an angiogenesis animal model. The angiogenic effects were confirmed in IL-5-deficient mice and addition of IL-5 antibody. HSP70-1 was identified via expression profiling following IL-5 stimulation. A siRNA knockdown of HSP70-1 suppressed angiogenic responses and eNOS phosphorylation induced by IL-5. HSP70-1 overexpression enhanced IL-5-induced angiogenic responses. In addition, IL-5-induced neo-vascular formation was verified in both HSP70-1 knockout and HSP70-1 transgenic mice. Furthermore, transcription factor AP-1 was a main factor in IL-5-induced HSP70-1 in response to ERK and AKT signaling pathway. Angiogenic responses induced by VEGF had no effect in either HSP70-1 siRNA in vitro or HSP70-1 knockout mice. IL-5-induced angiogenic responses depended on the binding of IL-5Rα. Our data demonstrate that binding of IL-5 to IL-5Rα receptors enhances angiogenic responses by stimulating the expression of HSP70-1 via the eNOS signaling pathway.
我们报告了白细胞介素 5（IL-5）作为一种血管生成激活剂的关键作用。IL-5 可促进 HUVEC 的增殖、迁移和集落管形成，与 ERK 和 AKT/eNOS 的磷酸化有关，并促进血管生成动物模型中的微血管发芽。在 IL-5 缺陷小鼠和添加 IL-5 抗体中证实了血管生成作用。IL-5 刺激后通过表达谱鉴定了 HSP70-1。HSP70-1 的 siRNA 敲低抑制了 IL-5 诱导的血管生成反应和 eNOS 磷酸化。HSP70-1 的过表达增强了 IL-5 诱导的血管生成反应。此外，在 HSP70-1 敲除和 HSP70-1 转基因小鼠中均验证了 IL-5 诱导的新血管形成。此外，AP-1 转录因子是 IL-5 诱导 HSP70-1 响应 ERK 和 AKT 信号通路的主要因素。VEGF 诱导的血管生成反应在 HSP70-1 siRNA 体外或 HSP70-1 敲除小鼠中均没有影响。IL-5 诱导的血管生成反应取决于 IL-5Rα 的结合。我们的数据表明，IL-5 与 IL-5Rα 受体的结合通过 eNOS 信号通路刺激 HSP70-1 的表达增强了血管生成反应。
