Hepatoma-derived growth factor stimulates smooth muscle cell growth and is expressed in vascular development

J Clin Invest. 2000 Mar;105(5):567-75. doi: 10.1172/JCI7497.


Hepatoma-derived growth factor (HDGF) is the first member identified of a new family of secreted heparin-binding growth factors highly expressed in the fetal aorta. The biologic role of HDGF in vascular growth is unknown. Here, we demonstrate that HDGF mRNA is expressed in smooth muscle cells (SMCs), most prominently in proliferating SMCs, 8-24 hours after serum stimulation. Exogenous HDGF and endogenous overexpression of HDGF stimulated a significant increase in SMC number and DNA synthesis. Rat aortic SMCs transfected with a hemagglutinin-epitope-tagged rat HDGF cDNA contain HA-HDGF in their nuclei during S-phase. We also detected native HDGF in nuclei of cultured SMCs, of SMCs and endothelial cells from 19-day fetal (but not in the adult) rat aorta, of SMCs proximal to abdominal aortic constriction in adult rats, and of SMCs in the neointima formed after endothelial denudation of the rat common carotid artery. Moreover, HDGF colocalizes with the proliferating cell nuclear antigen (PCNA) in SMCs in human atherosclerotic carotid arteries, suggesting that HDGF helps regulate SMC growth during development and in response to vascular injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta / embryology
  • Apoptosis / drug effects
  • Arteriosclerosis / metabolism
  • Cell Division / drug effects
  • Cells, Cultured
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Developmental
  • Growth Substances / biosynthesis
  • Growth Substances / pharmacology*
  • Hemagglutinins / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Mitogens / pharmacology
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / metabolism
  • Nuclear Proteins / metabolism
  • Proliferating Cell Nuclear Antigen / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • S Phase
  • Transfection
  • Tumor Cells, Cultured


  • Growth Substances
  • Hemagglutinins
  • Intercellular Signaling Peptides and Proteins
  • Mitogens
  • Nuclear Proteins
  • Proliferating Cell Nuclear Antigen
  • RNA, Messenger
  • hepatoma-derived growth factor