An autocrine function of nerve growth factor for cell cycle regulation of vascular endothelial cells

Biochem Biophys Res Commun. 2004 Jan 23;313(4):1009-14. doi: 10.1016/j.bbrc.2003.12.036.


Nerve growth factor (NGF) regulates maintenance, survival, and function of not only neuronal cells but also various kinds of non-neuronal cells. Here we clearly demonstrated that mouse aortic endothelial cells (AEC) produced bioactive NGF, and the production was enhanced by a proinflammatory cytokine, interleukin (IL)-1beta. AEC expressed both high affinity (TrkA) and low affinity (p75(NGFR)) receptors for NGF. Exogenously added NGF induced rapid phosphorylation of TrkA tyrosine kinase. Addition of anti-NGF neutralizing antibody resulted in an increase in the proportion of AEC in S and G(2)/M phases and in a hypodiploid range. Since the vascular endothelium plays a pivotal role in inflammatory conditions, these results strongly suggest that NGF, whose production is enhanced at the affected site, may contribute to maintenance, survival, and function of vascular endothelial cells by autocrine and/or paracrine mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Cycle / drug effects
  • Cell Cycle / physiology
  • Cell Division / drug effects
  • Cells, Cultured
  • DNA, Complementary / genetics
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology*
  • Gene Expression
  • Inflammation / physiopathology
  • Interleukin-1 / pharmacology
  • Mice
  • Nerve Growth Factor / antagonists & inhibitors
  • Nerve Growth Factor / pharmacology
  • Nerve Growth Factor / physiology*
  • Neutralization Tests
  • Receptor, Nerve Growth Factor / genetics
  • Receptor, Nerve Growth Factor / metabolism
  • Receptor, trkA / genetics
  • Receptor, trkA / metabolism


  • DNA, Complementary
  • Interleukin-1
  • Receptor, Nerve Growth Factor
  • Nerve Growth Factor
  • Receptor, trkA