A central role for hepatocyte growth factor in adipose tissue angiogenesis

Lauren N. Bell, Liying Cai, Brian H. Johnstone, Dmitry O. Traktuev, Keith L. March, Robert V. Considine

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)E336-E344
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume294
Issue number2
DOIs
StatePublished - Feb 1 2008

Keywords

  • 3T3-F442A
  • Neovascularization
  • Obesity
  • Platelet endothelial cell adhesion molecule-1
  • Tie-1

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

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