Down-regulation of p27kip1 increases proliferation of progenitor cells in adult rats.

Cyclin-dependent kinases (CDK) mediate the cell division cycle during G1 phase and CDK inhibitors negatively regulate the cell cycle. We investigated expression of the CDK inhibitor p27Kip1 and the effects of PI-3K/Akt on proliferation of progenitors in the subventricular zone of adult rat. Western blots and immunostaining revealed that 4 days after stroke, p27kip1 levels decreased and were absent in nuclei of the ipsilateral subventricular zone cells 7 days after stroke. Reduction in p27kip1 levels was concurrent with significant increases in BrdU immunoreactive cells in the subventricular zone. Treatment of stroke neurospheres with LY294002 significantly (p<0.05) reduced the numbers of neurospheres from 32 +/-5 in the stroke group to 14 +/- 3 in the stroke and LY294002 group. Collectively, our data suggest that stroke induced neural progenitor proliferation is mediated by down-regulation of p27Kip1 and activation of Akt.