The role of nerve growth factor in hyperosmolar stress induced apoptosis

J Cell Physiol. 2008 Jul;216(1):69-77. doi: 10.1002/jcp.21377.


Nerve growth factor (NGF) is a neurotrophic factor that plays an important role in the differentiation and growth of neuronal cells. It is also regarded as an inflammatory mediator in non-neuronal tissues under physiological stress conditions. The mechanisms of NGF production and its roles in hyperosmolar stress conditions have not been established. In this study, we show that NGF levels in cultured human corneal epithelial cells (HCECs) were up-regulated during hyperosmolar stress by IL-1beta, but not TNF-alpha. NF-kappaB activity, but not AP-1, increased significantly under hyperosmolar conditions, and NF-kappaB was involved in IL-1beta-induced NGF production. IL-1beta-induced NGF production reduced JNK phosphorylation and HCEC apoptosis. These changes were accompanied by down-regulated Bax and caspase-3, -8, -9 activities. NGF siRNA and the tyrosine kinase inhibitor K252a significantly enhanced Bax up-regulation. Thus, up-regulated NGF under hyperosmolar stress conditions may contribute, at least in part, to reduced HCEC apoptosis. This conclusion suggests that enhanced NGF expression may be beneficial in recovering corneal damage due to chronic hyperosmolar stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cornea / cytology*
  • Enzyme Inhibitors / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / physiology*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Signaling System / physiology
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nerve Growth Factor / genetics
  • Nerve Growth Factor / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Osmolar Concentration*
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, trkA / genetics
  • Receptor, trkA / metabolism
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / metabolism
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • Enzyme Inhibitors
  • Interleukin-1beta
  • NF-kappa B
  • NGFR protein, human
  • Nerve Tissue Proteins
  • Receptors, Nerve Growth Factor
  • Transcription Factor AP-1
  • Tumor Necrosis Factor-alpha
  • Nerve Growth Factor
  • Receptor, trkA
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases