Naringin enhances endothelial progenitor cell (EPC) proliferation and tube formation capacity through the CXCL12/CXCR4/PI3K/Akt signaling pathway
Naringin enhances endothelial progenitor cell (EPC) proliferation and tube formation capacity through the CXCL12/CXCR4/PI3K/Akt signaling pathway
复制标题
柚皮苷通过 CXCL12/CXCR4/PI3K/Akt 信号通路增强内皮祖细胞 (EPC) 增殖和管形成能力
DOI：
10.1016/j.cbi.2018.03.002
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发表时间：
2018-04-25
影响因子：
5.1
通讯作者：
Lv, Jianwei
中科院分区：
文献类型：
--
作者：
Zhao, Zhihu;Ma, Xinlong;Lv, Jianwei
内皮祖细胞（EPCs）已被证明参与了体内新生血管的生理性过程。由于越来越多的证据表明，柚皮苷作为中草药仙梨的主要活性成分，具有促进血管生成和抑制内皮细胞凋亡的作用，因此我们的研究旨在确定柚皮苷在内皮细胞内皮细胞增殖和成管能力中的作用，并探讨其可能的机制。从骨髓中分离EPCs，用柚皮苷处理。MTT法研究了EPCs在基质上的增殖和成管能力。Western blotting检测CXCL12及其受体（趋化因子受体4 (CXCR4)）和下游信号分子（Akt和磷酸化Akt (pAkt)）的蛋白水平。使用CXCR4拮抗剂（AMD3100）和磷脂酰肌醇3-激酶（PI3K）拮抗剂（LY294002）来表征其潜在机制。结果表明，柚皮苷诱导的EPC增殖在第3天达到最大，柚皮苷的最佳剂量为500 ng/ml。与对照组相比，柚皮苷促进了EPC成管能力，提高了CXCL12、CXCR4和pAkt水平（P < 0.05）。此外，AMD3100和LY294002显著降低了柚皮苷诱导的EPC成管能力。综上所述，我们在这里发现，柚皮苷增强的EPC增殖和管形成是通过CXCL12/CXCR4轴激活PI3K/Akt信号通路介导的，这表明柚皮苷可以作为一种新的治疗药物，具有应用于缺血性疾病治疗的潜力。
Endothelial progenitor cells (EPCs) have been shown to be involved in the process of physiological neovascularization in vivo. Because increasing evidence has indicated that naringin, a major active ingredient in the Chinese herb Drynaria fortunei, can promote angiogenesis and inhibit endothelial cell apoptosis, our study was designed to determine the role of naringin in EPC proliferation and tube formation capacity and examine the potential mechanism for these effects. EPCs were isolated from bone marrow and treated with naringin. An MTT assay was used to investigate EPC proliferation and the tube formation capacity of these EPCs, which were seeded on Matrigel. The protein levels of CXCL12, its receptor (chemokine receptor 4 (CXCR4)) and a downstream signaling molecule (Akt and phosphorylated Akt (pAkt)) were examined using Western blotting. A CXCR4 antagonist (AMD3100) and a phosphatidylinositol 3-kinase (PI3K) antagonist (LY294002) were used to characterize the underlying mechanisms. The results showed that naringin-induced EPC proliferation reached a maximum at day 3 and that the optimal dose of naringin was 500 ng/ml. Treatment with naringin facilitated the EPC tube formation capacity and increased the levels of CXCL12, CXCR4 and pAkt (P < 0.05) relative to those in the control group. Moreover, the naringin-induced EPC tube formation capacity was significantly attenuated by AMD3100 or LY294002. In conclusion, we showed here that the naringin-enhanced EPC proliferation and tube formation were mediated by the activation of the PI3K/Akt signaling pathway via the CXCL12/CXCR4 axis, which suggests that naringin could serve as a new therapeutic medicine and has the potential to be applied for the treatment of ischemic disease.