Vasoactive intestinal peptide: Mediator of laminin synthesis in cultured Schwann cells

Abstract

To learn more about neuropeptide‐induced glial responses which accompany axon regeneration, we studied effects of VIP on laminin production by cultured Schwann cells. Schwann cells were isolated from sciatic nerves of neonatal mice, purified, and incubated for 5 days in either control medium (DMEM + 15% FCS) or control medium containing 10−7 ‐10−11 M VIP. At 10−7 and 10−8 M VIP, laminin levels measured by enzyme‐linked immunosorbent assay were significantly higher (55% and 35%) than those in control cultures. Lower VIP concentrations (10−9 ‐10−11 M) produced smaller increases which were not significant. Low‐affinity VIP receptors which mediated this effect were demonstrated on Schwann cells by radioligand binding studies. The increased Schwann cell synthesis of laminin induced by VIP was blocked when either a VIP antagonist or a VIP receptor antagonist was added to the VIP‐containing incubation medium. In contrast to astrocytes, when Schwann cells were loaded with fura‐2, VIP did not increase cytosolic Ca2+. This indicates that Schwann cells and astrocytes may have different intracellular transduction pathways; their receptor subtypes also may differ. We suggest that the VIP‐induced increase in laminin synthesis which we have observed in cultured Schwann cells may also occur in vivo and might be an important component of axon‐Schwann cell interactions during nerve regeneration. © 1996 Wiley‐Liss, Inc.

Local administration of vasoactive intestinal peptide after nerve transection accelerates early myelination and growth of regenerating axons

“…Does VIP treatment accelerate regeneration in our model by upregulating Schwann cell synthesis of laminin‐2 and other laminin isoforms? The above evidence and our earlier findings ( Zhang et al, 1996 ) are consistent with this possibility.…”

“…There are 2 forms, VIP R 1 and VIP R 2 , which have different distributions in the CNS ( Usdin et al, 1994 ) . In the PNS, low affinity VIP receptors have been identified on cultured Schwann cells ( Zhang et al, 1996 ) and our subsequent studies, using both RT‐PCR and double enzyme digestion, indicated that these cultured Schwann cell receptors are type VIP R 2 , and not VIP R 1 (Lin P‐X et al, personal communication). Therefore, we suggest that VIP may promote regeneration, in part by its effects on Schwann cells.…”

“…To test whether a neuropeptide might be responsible for this effect, we exposed cultured Schwann cells to medium containing VIP. The response was a specific increase in laminin synthesis, which was shown to be associated with activation of low affinity VIP receptors ( Zhang et al, 1996 ) .…”

Impaired nerve regeneration and enhanced neuroinflammatory response in mice lacking pituitary adenylyl cyclase activating peptide

“…PACAP has been shown to induce neuritogenesis in at least three different primary cell culture models, sympathetic neuroblasts, cortical precursors and cerebellar granule cells (reviewed in (Waschek, 2002)) and to induce turning of growth cones of embryonic Xenopus spinal cord neurons (Guirland et al, 2003). Moreover, VIP has been shown to increase the in vitro Schwann cell production of laminin, which is a potential substrate for regenerating axons (Zhang et al, 1996). On the other hand, exogenous PACAP was unable to stimulate neurite outgrowth after nerve crush in nodose ganglia/vagal explants, a model which does not allow influx of immune cells into the injured nerve (Reimer et al, 1999).…”

Novel changes in gene expression following axotomy of a sympathetic ganglion: A microarray analysis

“…In addition to affecting neurons, VIP can also act on Schwann cells to increase the secretion of laminin (Q.L. Zhang et al, 1996), and on "resting" macrophages to stimulate the expression of IL-6 (Martinez et al, 1998).…”