FBP1 and p27kip1 expression after sciatic nerve injury: implications for Schwann cells proliferation and differentiation

J Cell Biochem. 2014 Jan;115(1):130-40. doi: 10.1002/jcb.24640.

Abstract

Far Upstream Element (FUSE) Binding Protein 1 (FBP1), first identified as a single-stranded DNA (ssDNA) binding protein that binds to the FUSE, could modulate c-myc mRNA levels and also has been shown to regulate tumor cell proliferation and replication of virus. Typically, FBP1 could active the translation of p27kip1 (p27) and participate in tumor growth. However, the expression and roles of FBP1 in peripheral system lesions and repair are still unknown. In our study, we found that FBP1 protein levels was relatively higher in the normal sciatic nerves, significantly decreased and reached a minimal level at Day 3, and then returned to the normal level at 4 weeks. Spatially, we observed that FBP1 had a major colocation in Schwann cells and FBP1 was connected with Ki-67 and Oct-6. In vitro, we detected the decreased level of FBP1 and p27 in the TNF-α-induced Schwann cells proliferation model, while increased expression in cAMP-induced Schwann cells differentiation system. Specially, FBP1-specific siRNA-transfected SCs did not show fine and longer morphological change after cAMP treatment and had a decreased motility compared with normal. At 3 days after cAMP treatment and SC/neuron co-cultures, p27 was transported to cytoplasm to form CDK4/6-p27 to participate in SCs differentiation. In conclusion, we speculated that FBP1 and p27 were involved in SCs proliferation and the following differentiation in the sciatic nerve after crush by transporting p27 from nucleus to cytoplasm.

Keywords: CIATIC NERVE INJURY; DIFFERENTIATION; FBP1; PROLIFERATION; SCHWANN CELLS; p27.

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Coculture Techniques
  • Cyclic AMP / pharmacology
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Cytoplasm / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Ki-67 Antigen / metabolism
  • Male
  • Nerve Crush
  • Protein Transport
  • RNA, Small Interfering
  • Rats
  • Rats, Sprague-Dawley
  • Schwann Cells / cytology
  • Schwann Cells / metabolism*
  • Sciatic Nerve / cytology
  • Sciatic Nerve / injuries*
  • Sciatic Nerve / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Cdkn1b protein, rat
  • DNA-Binding Proteins
  • FBP1 protein, rat
  • Ki-67 Antigen
  • RNA, Small Interfering
  • Tumor Necrosis Factor-alpha
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclic AMP