Acta Pharmacologica Sinica 2007 October; 28 (10): 1519-1530; doi: 10.1111/j.1745-7254.2007.00659.x

Aim: To have a better understanding of the expression and regulation of versican isoforms in neural precursor cells (NPC) and oligodendrogliogenesis.

Methods: By immunocytochemistry, RT-PCR, and real-time PCR, we examined the temporal expression of versican in NPC isolated from embryonic d 16 rats as well as in oligodendrocyte (OL) lineage cells induced to differentiate from NPC, which mimicked the oligodendrogliogenesis in vivo.

Results: We found that versican was constitutively expressed in NPC and their lineage cells, including neurons, astrocytes, and OL. In addition, 2 versican isoforms, V1/V0 and V2, were found to express at low levels in NPC, but at significantly higher levels in OL lineage cells. The peak expression of versican V2 was found at the oligodendrocyte precursor cell stage. Furthermore, the treatment of 2 pro-inflammatory cytokines, TNF-α and IFN-γ, enhanced the transcription of versican V2 in NPC in a dose-dependent manner, but showed no effect on V1/V0 expression.

Conclusion: Taken together, our results demonstrate that versican, particularly the inhibitory V2 isoform, is increasingly expressed in OL lineage cells induced to differentiate from NPC. An increase in versican V2 expression after cytokine stimulation implies the interplay between the injury-induced upregulation of inflammatory cytokines and chondroitin sulfate proteoglycan-mediated inhibition of axonal regeneration after central nervous system injury.

Keywords: chondroitin sulfate proteoglycans; neural precursor cells; oligodendrocyte precursor cells; oligodendrocytes; pro-inflammatory cytokines; versican