A central role for hepatocyte growth factor in adipose tissue angiogenesis
A central role for hepatocyte growth factor in adipose tissue angiogenesis
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DOI：
10.1152/ajpendo.00272.2007
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发表时间：
2008-02-01
影响因子：
5.1
通讯作者：
Considine, Robert V.
中科院分区：
文献类型：
--
作者：
Bell, Lauren N.;Cai, Liying;Considine, Robert V.
肝细胞生长因子（HGF）是一种有效的促有丝分裂和血管生成因子，产生于人体脂肪组织。在这项研究中，我们使用3 T3-F442 A前脂肪细胞研究肝细胞生长因子的贡献，血管生成在体内脂肪垫发展模型。如在人脂肪细胞中观察到的，HGF由3 T3-F442 A前脂肪细胞和成熟脂肪细胞合成和分泌。用小干扰RNA敲低HGF使3 T3-F442 A前脂肪细胞的HGF mRNA表达减少82.3 +/- 4.2%，蛋白分泌减少82.9 +/- 1.4%。HGF沉默导致内皮祖细胞向3 T3-F442 A条件培养基迁移的体外减少70.5 +/- 19.0%。注射到小鼠皮下的3 T3-F442 A前脂肪细胞形成含有成熟的充满脂质的脂肪细胞和功能性脉管系统的脂肪垫。在注射后72小时，在HGF沉默的3 T3-F442 A脂肪垫中，内皮细胞基因TIE-1和血小板内皮细胞粘附分子（PECAM）-1的表达分别降低了94.4 +/-2.2%和91.5 +/-2.5%。在体外或体内，HGF的敲低对3 T3-F442 A前脂肪细胞向成熟脂肪细胞的分化没有影响。在肝细胞生长因子过度表达转基因小鼠皮肤下的脂肪垫中，TIE-1和PECAM-1 mRNA在注射后72小时分别增加了16.5倍和21.4倍。基因表达的增加与发育中的脂肪垫中内皮细胞迁移的免疫组化证据相关。这些数据表明，HGF在调节脂肪组织中的血管生成中具有核心作用。
Hepatocyte growth factor (HGF) is a potent mitogenic and angiogenic factor produced in human adipose tissue. In this study, we use 3T3-F442A preadipocytes to study the contribution of HGF to angiogenesis in an in vivo fat pad development model. As observed for human adipocytes, HGF is synthesized and secreted by 3T3-F442A preadipocytes and mature adipocytes. HGF knockdown with small-interfering RNA reduced HGF mRNA expression 82.3 +/- 4.2% and protein secretion 82.9 +/- 1.4% from 3T3- F442A preadipocytes. Silencing of HGF resulted in a 70.5 +/- 19.0% reduction in endothelial progenitor cell migration to 3T3-F442A-conditioned medium in vitro. 3T3-F442A preadipocytes injected under the skin of mice form a fat pad containing mature, lipid-filled adipocytes and a functional vasculature. At 72 h postinjection, expression of the endothelial cell genes TIE-1 and platelet endothelial cell adhesion molecule ( PECAM)-1 was decreased 94.4 +/- 2.2 and 91.5 +/- 2.5%, respectively, in 3T3-F442A fat pads with HGF silencing. Knockdown of HGF had no effect on differentiation of 3T3- F442A preadipocytes to mature adipocytes in vitro or in vivo. In developing fat pads under the skin of HGF overexpressing transgenic mice, TIE-1 and PECAM-1 mRNA was increased 16.5- and 21.4-fold, respectively, at 72 h postinjection. The increase in gene expression correlated with immunohistochemical evidence of endothelial cell migration in the developing fat pad. These data suggest that HGF has a central role in regulating angiogenesis in adipose tissue.