A central role for hepatocyte growth factor in adipose tissue angiogenesis

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

Research output: Contribution to journalArticle

46 Citations (Scopus)

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
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume294
Issue number2
DOIs
StatePublished - Feb 2008

Fingerprint

Hepatocyte Growth Factor
Adipose Tissue
Tissue
Adipocytes
Fats
Endothelial cells
CD31 Antigens
Cell Movement
Endothelial Cells
Skin
Messenger RNA
Angiogenesis Inducing Agents
Conditioned Culture Medium
Small Interfering RNA
Transgenic Mice
Gene expression
Genes
Lipids
Gene Expression

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

A central role for hepatocyte growth factor in adipose tissue angiogenesis. / Bell, Lauren N.; Cai, Liying; Johnstone, Brian H.; Traktuev, Dmitry; March, Keith L.; Considine, Robert.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 294, No. 2, 02.2008.

Research output: Contribution to journalArticle

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