Hepatoma-derived growth factor is a pulmonary endothelial cell-expressed angiogenic factor
Hepatoma-derived growth factor is a pulmonary endothelial cell-expressed angiogenic factor
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DOI：
10.1152/ajplung.00427.2003
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发表时间：
2004-06-01
影响因子：
4.9
通讯作者：
Tucker, A
中科院分区：
文献类型：
--
作者：
Everett, AD;Narron, JV;Tucker, A
肝细胞源性生长因子（HDGF）先前被认为是一种发育调节的心血管和肾脏基因，对血管平滑肌和主动脉内皮细胞具有促有丝分裂作用。由于平滑肌和内皮细胞的相互作用是血管形成所必需的，因此我们检查了 HDGF 是否在血管生成中发挥作用。根据免疫组织化学，HDGF 在非肌肉化的、形成胎儿肺血管的内皮细胞中高表达。 HDGF 也在小（20μm）成熟动脉和静脉的内皮细胞中表达。 Western免疫印迹结果显示，体外人肺微血管内皮细胞高表达HDGF。 HDGF 的腺病毒过表达对无血清培养基中的人肺微血管内皮细胞具有促有丝分裂作用，刺激溴脱氧尿苷 (BrdU) 摄取增加 1.75 倍，细胞迁移增加两倍。在鸡绒毛尿囊膜 (CAM) 中，外源重组 HDGF 显着刺激血管形成，并以剂量依赖性方式将 CAM 内的细胞重组为更紧凑、线性的排列，类似于管的形成。根据使用转化生长因子-βII受体抗体和作为细胞增殖标记的BrdU对内皮细胞进行的双重免疫染色，外源HDGF选择性刺激内皮细胞对BrdU的摄取。 HDGF 还激活特定的 ERK1/2 信号传导，并且与 VEGF SAPK/JNK、Akt 介导的途径不重叠。我们得出的结论是，HDGF 是体内高表达的血管内皮细胞蛋白，并且是一种有效的内皮细胞有丝分裂原，并且通过与 VEGF 不同的机制调节内皮细胞迁移。
Hepatoma-derived growth factor ( HDGF) was previously identified as a developmentally regulated cardiovascular and renal gene that is mitogenic for vascular smooth muscle and aortic endothelial cells. As reciprocal interactions of smooth muscle and endothelial cells are necessary for vascular formation, we examined whether HDGF plays a role in angiogenesis. According to immunohistochemistry, HDGF was highly expressed in endothelial cells of nonmuscularized, forming blood vessels of the fetal lung. HDGF was also expressed in endothelial cells of small ( 20 mum) mature arteries and veins. By Western immunoblotting, HDGF was highly expressed by human pulmonary microvascular endothelial cells in vitro. Adenoviral overexpression of HDGF was mitogenic for human pulmonary microvascular endothelial cells in serum-free medium, stimulating a 1.75-fold increase in bromodeoxyuridine ( BrdU) uptake and a twofold increase in cell migration. With the chick chorioallantoic membrane ( CAM), a biologic assay for angiogenesis, exogenous recombinant HDGF significantly stimulated blood vessel formation and a dose-dependent reorganization of cells within the CAM into a more compact, linear alignment reminiscent of tube formation. According to double immunostaining for endothelial cells with a transforming growth factor-betaII receptor antibody and BrdU as a marker of cell proliferation, exogenous HDGF selectively stimulated endothelial cell BrdU uptake. HDGF also activated specific ERK1/2 signaling and did not overlap with VEGF SAPK/JNK, Akt-mediated pathways. We conclude that HDGF is a highly expressed vascular endothelial cell protein in vivo and is a potent endothelial mitogen and regulator of endothelial cell migration by mechanisms distinct from VEGF.