Calcitonin gene-related peptide promotes Schwann cell proliferation.

Abstract

Abstract. Schwann cells in culture divide in response to defined mitogens such as PDGF and glial growth factor (GGF), but proliferation is greatly enhanced if agents such as forskolin, which increases Schwann cell intracellular cAMP, are added at the same time as PDGF or GGF (Davis, J. B., and P. Stroobant. 1990. J. Cell Biol. 110:1353-1360. The effect of forskolin is probably due to an increase in numbers of PDGF receptors (Weinmaster, G., and G. Lemke. 1990. .Neuropeptides and/$-adrenergic agonists have been reported to have no effect on potentiating the mitogenic response of either PDGF or GGE We show that the neuropeptide calcitonin gene-related peptide (CGRP) increases Schwann cell cAMP levels, but the cells rapidly desensitize. We therefore stimulated the cells in pulsatile fashion to partly overcome the effects of desensitization and show that CGRP can synergize with PDGF to stimulate Schwann cell proliferation, and that CGRP is as effective as forskolin in the pulsatile regime.CGRP is a good substrate for the neutral endopeptidase 24.11. Schwann cells in vivo have this protease on their surface, so the action of CGRP could be terminated by this enzyme and desensitization prevented. We therefore suggest that CGRP may play an important role in stimulating Schwann cell proliferation by regulating the response of mitogenic factors such as PDGE T nEaE are two circumstances in which Schwann ceils, the glial cells of peripheral nerves, proliferate: during development and after nerve injury. During development, they proliferate as they migrate out along growing axons (Eccleston, 1992). After nerve injury, they undergo two waves of proliferation: one occurs acutely, adjacent to the injury site, whereas the second occurs over a prolonged period as the nerve undergoes Wallerian degeneration and regeneration and extends distally from the injury site (Fawcett and Keynes, 1990). Although it is still not clear how Schwann cell division is controlled in vivo, there has been considerable effort to identify the mitogens that regulate the proliferation of rat sciatic nerve Schwann cells in culture. PDGF, FGF-1 and FGF-2, TGF-/~, and glial growth factor (GGF) m have all been shown to promote the proliferation of these ceils. In addition, Schwann cells in culture respond to

Innervation of ectopic endometrium in a rat model of endometriosis

“…Thus, they could play a role, along with sympathetic nerves, in regulating the vasculature of the cyst. Finally, there is evidence that both SP and CGRP have mitogenic effects on endothelial and Schwann cells (44,45).…”

Nf1-Deficient Mouse Schwann Cells Are Angiogenic and Invasive and Can Be Induced To Hyperproliferate: Reversion of Some Phenotypes by an Inhibitor of Farnesyl Protein Transferase

“…A neuropeptide, calcitonin gene-related peptide (CGRP), has been proposed as an in vivo candidate for cAMP control of Schwann cell development. In culture, exposure to CGRP increases intracellular cAMP in Schwann cells and synergizes with a Schwann cell mitogen to stimulate proliferation (10). CGRP is expressed by sensory and motor neurons (1,46) and is expressed by axons within neurofibromas (68).…”

Matrix metalloproteinase mediated degradation of basement membrane proteins in Trembler J neuropathy nerves

“…Immunopanning CD11b-positive immune cells Antibody-coated plates were prepared by incubating 6-cm culture dishes with 30 lg of anti-rat IgG (Sigma) in 2 mL of carbonate/ bicarbonate buffer (pH 9.6), overnight at 4°C on a rotating platform (Cheng et al 1995). The plates were rinsed with PBS and incubated with anti-CD11b antibody (Serotec) for 1 h at a concentration of 1 lg/mL in PBS/0.1% bovine serum albumin (BSA).…”

“…Because the tissue fixation and permeabilization procedures for the MMP and the CD11b antibodies are not compatible (see Experimental procedures), CD11b-positive cells were isolated from the nerves by positive immunopanning (Cheng et al 1995). Isolated CD11b-positive cells from TrJ nerve homogenates were allowed to adhere to glass coverslips overnight and labeled with polyclonal antibodies against MMP-2 (Fig.…”