Osteopontin (Eta-1) and fibroblast growth factor-2 cross-talk in angiogenesis
Osteopontin (Eta-1) and fibroblast growth factor-2 cross-talk in angiogenesis
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DOI：
10.4049/jimmunol.171.2.1085
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发表时间：
2003-07-15
影响因子：
4.4
通讯作者：
Presta, M
中科院分区：
文献类型：
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作者：
Leali, D;Dell'Era, P;Presta, M
细胞因子/细胞外基质蛋白骨桥蛋白（OPN/Eta-1）是细胞免疫和炎症的重要组成部分。它还充当内皮细胞的生存因子、细胞粘附因子和趋化因子。在这里，消减抑制杂交显示，与亲代细胞相比，转染血管生成成纤维细胞生长因子-2 (FGF2) 的去血清小鼠主动脉内皮 (MAE) 细胞过表达 OPN。通过对过表达 FGF2 的内皮细胞的不同克隆和用重组生长因子处理的内皮细胞中的条件培养基进行 Northern 印迹和 Western 印迹分析证实了这一点。在体内，FGF2 引起鸡胚绒毛尿囊膜 (CAM) 和小鼠皮下新形成的内皮细胞中 OPN 的表达。基质胶塞植入物。重组 OPN (rOPN)、融合蛋白 GST-OPN 和缺失突变体 GST-DeltaRGD-OPN 在 CAM 测定中具有血管生成作用。移植到 CAM 上的 OPN 转染的 MAE 细胞也能触发血管生成。 OPN 驱动的新生血管形成独立于内皮 α(v)β(3) 整合素的参与，并且总是与大量单核细胞浸润的出现同时发生。因此，rOPN、GST-OPN、GST-DeltaRGD-OPN 和 OPN 过表达 MAE 细胞的条件培养基对分离的人单核细胞具有趋化性。此外，rOPN 通过诱导血管生成细胞因子 TNF-α 和 IL-8 的表达，在人单核细胞中触发促血管生成表型。 OPN 介导的促血管生成单核细胞的募集可能代表了炎症、伤口愈合和肿瘤生长期间 FGF2 诱导的新血管形成的放大机制。
The cytokine/extracellular matrix protein osteopontin (OPN/Eta-1) is an important component of cellular immunity and inflammation. It also acts as a survival, cell-adhesive, and chemotactic factor for endothelial cells. Here, subtractive suppression hybridization showed that serum-deprived murine aortic endothelial (MAE) cells transfected with the angiogenic fibroblast growth factor-2 (FGF2) overexpress OPN compared with parental cells. This was confirmed by Northern blotting and Western blot analysis of the conditioned media in different clones of endothelial cells overexpressing FGF2 and in endothelial cells treated with the recombinant growth factor. In vivo, FGF2 caused OPN expression in newly formed endothelium of the chick embryo chorioallantoic membrane (CAM) and of murine s.c. Matrigel plug implants. Recombinant OPN (rOPN), the fusion protein GST-OPN, and the deletion mutant GST-DeltaRGD-OPN were angiogenic in the CAM assay. Angiogenesis was also triggered by OPN-transfected MAE cells grafted onto the CAM. OPN-driven neovascularization was independent from endothelial alpha(v)beta(3) integrin engagement and was always paralleled by the appearance of a massive mononuclear cell infiltrate. Accordingly, rOPN, GST-OPN, GST-DeltaRGD-OPN, and the conditioned medium of OPN-overexpressing MAE cells were chemotactic for isolated human monocytes. Also, rOPN triggered a proangiogenic phenotype in human monocytes by inducing the expression of the angiogenic cytokines TNF-alpha and IL-8. OPN-mediated recruitment of proangiogenic monocytes may represent a mechanism of amplification of FGF2-induced neovascularization during inflammation, wound healing, and tumor growth.