Peripheral nerve injury induces down-regulation of Foxo3a and p27kip1 in rat dorsal root ganglia.

ABSTRACT

FOXO3a, as a forkhead transcription factor, can control cell cycle through transcriptionally down-regulating p27(kip1) level, which is a key regulator of the mammalian cell cycle and a good candidate to regulate multiple aspects of neurogenesis. To elucidate their expression and function in nervous system lesion and repair, we performed an acute sciatic nerve crush model and studied differential expressions of Foxo3a and p27(kip1) in lumbar dorsal root ganglia. Temporally, Foxo3a protein level was reduced 1 day after injury, and following Foxo3a down-regulation, p27(kip1) mRNA and protein levels were also decreased after injury. Spatially, decreased levels of Foxo3a and p27(kip1) were predominant in neurons and glial cells, which were regenerating axons and largely proliferated after injury, respectively. Together with previous reports, we hypothesized decreased levels of Foxo3a and p27(kip1) in lumbar dorsal root ganglia were implicated in axonal regeneration and the proliferation of glial cells after sciatic nerve injury.