TGF-β1 is critical for Wallerian degeneration after rat sciatic nerve injury

Neuroscience. 2015 Jan 22:284:759-767. doi: 10.1016/j.neuroscience.2014.10.051. Epub 2014 Nov 4.

Abstract

Wallerian degeneration (WD) is a process of axonal degeneration distal to the injury site followed by a robust regenerative response. It involves degeneration and regeneration which can be directly induced by nerve injury and activated by transcription factors. Although WD has been studied extensively, the precise mechanisms of transcription factors regulating WD are still elusive. In this study, we reported the effect of transforming growth factor-β1 (TGF-β1) on WD after rat sciatic nerve injury. The data showed that TGF-β1 may express in injured rat sciatic nerve and cultured Schwann cells (SCs). Knock down of TGF-β1 expressions resulted in the reduction of SC proliferation and apoptosis, up regulation of cytokines and Smad2, 4. Enhanced expression of TGF-β1 could promote SC proliferation and apoptosis, down regulation of cytokines and Smad2, 4. Altered expressions of TGF-β1 may affect Smad and AKT but not c-Jun and extracellular regulated protein kinase (ERK) pathways. Our results revealed the role of TGF-β1 on WD and provided the basis for the molecular mechanisms of TGF-β1-regulated nerve degeneration and/or regeneration.

Keywords: Schwann cells; Wallerian degeneration; nerve regeneration; rat; signal pathway; transforming growth factor-β1 (TGF-β1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Cytokines / metabolism
  • Disease Models, Animal
  • MAP Kinase Signaling System / physiology
  • Male
  • Proto-Oncogene Proteins c-akt / metabolism
  • Random Allocation
  • Rats, Sprague-Dawley
  • Schwann Cells / metabolism
  • Schwann Cells / pathology
  • Sciatic Nerve / injuries*
  • Sciatic Nerve / metabolism*
  • Sciatic Nerve / pathology
  • Sciatic Neuropathy / metabolism*
  • Sciatic Neuropathy / pathology
  • Smad2 Protein / metabolism
  • Smad4 Protein / metabolism
  • Transforming Growth Factor beta1 / metabolism*
  • Up-Regulation / physiology
  • Wallerian Degeneration / metabolism*
  • Wallerian Degeneration / pathology

Substances

  • Cytokines
  • Smad2 Protein
  • Smad2 protein, rat
  • Smad4 Protein
  • Smad4 protein, rat
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • Proto-Oncogene Proteins c-akt