Early changes in gene expression in the dorsal root ganglia after transection of the sciatic nerve; effects of amphiregulin and PAI-1 on regeneration.

Abstract

To characterize the gene activity that may be required for neuronal survival and regeneration, we used the Affymetrix GeneChip Mu74A to screen 12000 genes and expressed sequence tag (EST) mRNA from L4 and L5 mouse dorsal root ganglia (DRG) 12 h and 24 h after sciatic nerve transection. At 12 h, we found 17 upregulated transcripts, and at 24 h, 49 that met our criteria of a significant 2-fold increase in expression. The alterations included a total of eight transcription factors and several genes associated with TGF-beta- and IL-6-mediated signaling. Two of the changes, amphiregulin and plasminogen activator inhibitor-1 (PAI-1), were confirmed by real-time quantitative PCR (QPCR). Addition of amphiregulin (20 ng/ml) to organ-cultured DRG stimulated axonal outgrowth while PAI-1 (20 nM) inhibited migration of Schwann cells from the ganglia