Nidogen is a prosurvival and promigratory factor for adult Schwann cells

Abstract

Schwann cells provide a favorable microenvironment for successful regeneration of the injured peripheral nerve. Even though the roles of extracellular matrix proteins in the Schwann cell physiology have long been studied, the precise function of nidogen, a ubiquitous component of the basal lamina, in Schwann cells is unknown. In this study, we show that the protein and mRNA messages for nidogens are upregulated in the sciatic nerve after sciatic nerve transection. We demonstrate that recombinant nidogen-1 increased the process formation of Schwann cells cultured from adult rat sciatic nerves and that nidogen-1 prevented Schwann cells from serum-deprivation-induced death. In addition, nidogen-1 promoted spontaneous migration of Schwann cells in twoindependent migration assays. The Schwann cell responses to the recombinant nidogen-1 were specific because the nidogen-binding ectodomain of tumor endothelial marker 7 inhibited the nidogen responses without affecting Schwann cell response to laminin. Finally, we found that b1 subunitcontaining integrins play a key role in the nidogen-induced process formation, survival, and migration of Schwann cells. Altogether, these results indicate that nidogen has a prosurvival and promigratory activity on Schwann cells in the peripheral nerve.

Basement membrane protein nidogen‐1 shapes hippocampal synaptic plasticity and excitability

“…Brain malformations including exencephaly and layering abnormalities, both presumably due to meningeal defects, are known to occur in the absence of the nidogen-binding site on the laminin g1 chain or the absence of the laminin a5 chain (Miner et al, 1998). Furthermore, nidogen-1 is necessary for axonal sprouting at least peripherally (Lee et al, 2007). However, we did not observe any major layering or meningeal defects, indeed, changes of BMs are considered to be minimal Murshed et al, 2000).…”

Nidogens—Extracellular matrix linker molecules

“…Nidogen immunoreactivity is retained in endoneural tubes undergoing Wallerian degeneration and indeed increased levels of protein and mRNA occur after section of the sciatic nerve (Lee et al, 2007). This maybe biologically relevant as nidogen-1 has been shown to enhance survival, process formation and migration of Schwann cells, events induced by b1 integrin receptors and possibly modulated by TEM7 (Lee et al, 2007).…”

Expression changes and bioinformatic analysis of Wallerian degeneration after sciatic nerve injury in rat

“…The molecules that were significantly up-or down-regulated after such injury are known to modulate the signal pathways in key networks [15,[29][30][31][32] . It is supposed that the key networks play roles in Schwann cell activation and proliferation as well as WD and subsequent regeneration [33][34][35] . The data also suggested that the functional group of transcriptional regulators indicated in the changes of expression of these genes may be an essential prerequisite for peripheral nerve degeneration and/or regeneration.…”