Exogenous basic fibroblast growth factor inhibits ER stress-induced apoptosis and improves recovery from spinal cord injury

CNS Neurosci Ther. 2013 Jan;19(1):20-9. doi: 10.1111/cns.12013. Epub 2012 Oct 20.

Abstract

Aim: To investigate the mechanism of endoplasmic reticulum (ER) stress-induced apoptosis as well as the protective action of basic fibroblast growth factor (bFGF) both in vivo and in vitro.

Methods and results: ER stress-induced apoptosis was involved in the injuries of spinal cord injury (SCI) model rat. bFGF administration improved the recovery and increased the survival of neurons in spinal cord lesions in model rat. The protective effect of bFGF is related to the inhibition of CHOP, GRP78 and caspase-12, which are ER stress-induced apoptosis response proteins. bFGF administration also increased the survival of neurons and the expression of growth-associated protein 43 (GAP43), which is related to neural regeneration. The protective effect of bFGF is related to the activation of downstream signals, PI3K/Akt/GSK-3β and ERK1/2, especially in the ER stress cell model.

Conclusions: This is the first study to illustrate that the role of bFGF in SCI recovery is related to the inhibition of ER stress-induced cell death via the activation of downstream signals. Our work also suggested a new trend for bFGF drug development in central neural system injuries, which are involved in chronic ER stress-induced apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspase 12 / metabolism
  • Disease Models, Animal
  • Endoplasmic Reticulum Stress / drug effects*
  • Female
  • Fibroblast Growth Factor 2 / therapeutic use*
  • GAP-43 Protein / metabolism
  • Heat-Shock Proteins / metabolism
  • In Situ Nick-End Labeling
  • Locomotion / drug effects
  • Neurons / drug effects*
  • Neurons / metabolism
  • PC12 Cells
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects*
  • Severity of Illness Index
  • Signal Transduction / drug effects
  • Spinal Cord Injuries* / drug therapy
  • Spinal Cord Injuries* / pathology
  • Spinal Cord Injuries* / physiopathology
  • Time Factors
  • Transcription Factor CHOP / metabolism
  • Up-Regulation / drug effects

Substances

  • Ddit3 protein, rat
  • GAP-43 Protein
  • GRP78 protein, rat
  • Heat-Shock Proteins
  • Fibroblast Growth Factor 2
  • Transcription Factor CHOP
  • Proto-Oncogene Proteins c-akt
  • Casp12 protein, rat
  • Caspase 12