Platelet‐derived growth factor and regulation of schwann cell proliferation in vivo

Abstract

To examine the role of platelet-derived growth factor (PDGF) in the in vivo regulation of Schwann cell proliferation, steady-state levels of mRNAs encoding PDGF A and B chains, and PDGF alpha and beta receptors were measured in immature and adult rat sciatic nerves and in cultured rat Schwann cells. PDGF B chain and PDGF beta receptor mRNAs are present in immature rat sciatic nerves and to a lesser extent in adult rat nerves. Short-term cultures of neonatal rat Schwann cells express PDGF beta receptor mRNA, but not PDGF B chain mRNA, and are stimulated to synthesize DNA by addition of PDGF BB to the medium. These data indicate that PDGF BB is a developmentally regulated paracrine growth factor for rat Schwann cells. Very long-term cultures of rat Schwann cells, which have lost normal dependence on exogenous growth factors, express PDGF B chain mRNA as well as mRNAs encoding the PDGF alpha and beta receptors, suggesting that, under these circumstances, PDGF BB also act as an autocrine growth factor. PDGF A chain mRNA is present in both immature and adult rat sciatic nerves and is expressed by primary and secondary cultures of rat Schwann cells as well. However, because the abundance of PDGF alpha receptor mRNA is very low in rat Schwann cells, PDGF AA is not likely to be a significant autocrine growth factor for rat Schwann cells.

Merlin regulates transmembrane receptor accumulation and signaling at the plasma membrane in primary mouse Schwann cells and in human schwannomas

“…Following the release from the block, progression of ts045VSV-GFP and ErbB2 in transport vesicles was followed by immunofluorescence. Colocalization with several other receptors is presented in Supplementary Figure 4. proliferation (Hardy et al, 1992;Syroid et al, 1999;Cheng et al, 2000;Lobsiger et al, 2000). We showed that these receptors are also upregulated in Nf2 À/À SCs, in mouse Nf2-mutant nerves and in human schwannomas.…”

Cell death in the Schwann cell lineage and its regulation by neuregulin.

“…Response to FGF-2 as a survival factor in postnatal Schwann cells may depend on coadministration of Fsk, which is known, through elevation of intracellular cAMP, to upregulate growth factor receptor expression (25) and which is required for optimal stimulation of postnatal rat Schwann cell proliferation by FGF-2 (24). These same considerations apply to PDGF-BB, which also can act as a mitogen for postnatal rat Schwann cells (9,22,23), but whose mitogenic effect also depends on cAMP elevation (25).…”

“…Three growth factors, namely FGF-2, PDGF-BB, and NRG-,B1, are mitogenic for Schwann cells in vitro, an activity which is potentiated by the Fsk-mediated elevation of intracellular levels of cAMP (9,16,(22)(23)(24). Moreover, FGF-2 and NRG-131 can act as survival factors for Schwann cell precursors in vitro (7,18), whereas PDGF-AA can mediate the survival of oligodendrocytes and their 0-2A progenitors both in vitro and in vivo (20).…”

ErbB2 Signaling in Schwann Cells Is Mostly Dispensable for Maintenance of Myelinated Peripheral Nerves and Proliferation of Adult Schwann Cells after Injury

“…It remains to be seen whether interrupting this signaling pathway will have an impact on proliferation of adult Schwann cells after injury. Other mitogens that may play a role include PDGF (Hardy et al, 1992), NT-3 (neurotrophin 3) (Funakoshi et al, 1993), and IGF (Sondell et al, 1997).…”