Post-transcriptional regulation of PDGFα-receptor in O-2A progenitor cells.

latelet-derived growth factor alpha-receptor (PDGFαR) mediated signaling plays a key role in the development of glial cells of the central nervous system. In vivo and in vitro studies show that PDGFαR is actively expressed in proliferative and motile oligodendrocyte type-2 astrocyte (O-2A) glial progenitor cells. However, PDGFαR expression is barely detectable in mature glial cells. The exact mechanism underlying the loss of PDGFαR expression is unknown. In this study, we employed a rat brain-derived O-2A glial progenitor cell line, CG4 as a culture model to investigate signals capable of inhibiting PDGFαR gene expression. PDGFαR mRNA levels decreased significantly as CG4 cells differentiated into both oligodendrocyte and astrocyte lineages. We showed that inhibition of PDGFαR expression was promoted by prostaglandin E2 via protein kinase A activation. Both cAMP analogs (db-cAMP and 8'bromo-cAMP) and adenylate cyclase activator (forskolin) were potent suppressors of PDGFαR expression in CG4 cells. This inhibitory effect resulted from an increased destabilization of PDGFαR mRNA instead of a decreased PDGFαR gene transcription. Importantly, db-cAMP failed to reduce PDGFαR mRNA levels in several PDGFαR over-expressing human glioma cell lines. Together, these results suggest that cAMP-dependent pathway played a key regulatory role in controlling PDGFαR mRNA levels during normal glial development, and that a breakdown in the cross talk between cAMP and PDGF pathways may underlie the uncontrolled proliferation and immature differentiation state in the glial tumors.