scholarly journals Coordinate control of axon defasciculation and myelination by laminin-2 and -8

2005 ◽  
Vol 168 (4) ◽  
pp. 655-666 ◽  
Author(s):  
Dongren Yang ◽  
Jesse Bierman ◽  
Yukie S. Tarumi ◽  
Yong-Ping Zhong ◽  
Reshma Rangwala ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Dominant Role ◽  
Pathogenic Mechanism ◽  
Structural Defects ◽  
Autocrine Factors ◽  
Coordinate Control

Schwann cells form basal laminae (BLs) containing laminin-2 (Ln-2; heterotrimer α2β1γ1) and Ln-8 (α4β1γ1). Loss of Ln-2 in humans and mice carrying α2-chain mutations prevents developing Schwann cells from fully defasciculating axons, resulting in partial amyelination. The principal pathogenic mechanism is thought to derive from structural defects in Schwann cell BLs, which Ln-2 scaffolds. However, we found loss of Ln-8 caused partial amyelination in mice without affecting BL structure or Ln-2 levels. Combined Ln-2/Ln-8 deficiency caused nearly complete amyelination, revealing Ln-2 and -8 together have a dominant role in defasciculation, and that Ln-8 promotes myelination without BLs. Transgenic Ln-10 (α5β1γ1) expression also promoted myelination without BL formation. Rather than BL structure, we found Ln-2 and -8 were specifically required for the increased perinatal Schwann cell proliferation that attends myelination. Purified Ln-2 and -8 directly enhanced in vitro Schwann cell proliferation in collaboration with autocrine factors, suggesting Lns control the onset of myelination by modulating responses to mitogens in vivo.

scholarly journals Neuron Regeneration and Proliferation Effects of Danshen and Tanshinone IIA

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Jui-Lung Shen ◽  
Yueh-Sheng Chen ◽  
Jing-Ying Lin ◽  
Yun-Chen Tien ◽  
Wen-Huang Peng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Map Kinases ◽  
Mapk Signaling ◽  
Tanshinone Iia ◽  
Dependent Manner ◽  
Neuron Regeneration

This study evaluates the proliferative effects of danshen and its monomer extract, tanshinone IIA, on Schwann cell proliferation. A piece of silicone rubber was guided across a 15-mm gap in the sciatic nerve of a rat. This nerve gap was then filled with different concentrations of danshen (0–100 mg/mL). The results showed that danshen increased the expressions of uPA, cyclin D1, E and ERK, JNK, and P38 MAP kinases via the FGF-2 signaling pathway in a dose-dependent manner. RSC96, Schwann cells were also administered with danshen (0, 20, 40, 60, 80, and 100 μg/mL) and tanshinone IIA (0, 2, 4, 6, 8, and 10 μg/mL). In lower concentrations, danshen and tanshinone IIA exhibited an apparent effect on Schwann cells. Similar effects were also demonstrated in the FGF-2-uPA regulating cascade and cell cycle proliferative protein results. Schwann cell migration was elevated as well. We used MAPK-signaling chemical inhibitors and identified the proliferative effects of danshen and tanshinone IIA as MAPK-signaling dependent. The results from thein vitrosystems indicate that danshen and tanshinone IIA can be used to induce Schwann cell proliferation, andin vivoresults potentially suggest that danshen and tanshinone IIA might enhance neuron regeneration.

Axonal signalling and the making of olfactory ensheathing cells: a hypothesis

2006 ◽  
Vol 2 (3) ◽  
pp. 217-224 ◽  
Author(s):  
KONSTANTIN WEWETZER ◽  
GUDRUN BRANDES
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Specific Interaction ◽  
Neurotrophin Receptor ◽  
Olfactory Ensheathing Cells ◽  
Experimental Conditions ◽  
Neural Repair ◽  
Ensheathing Cells

Olfactory ensheathing cells (OECs) are Schwann cell-like glial cells of the olfactory system that promote neural repair under experimental conditions. It is a matter of debate in how far OECs resemble Schwann cells and whether they possess specific properties. Although OECs have been characterized mainly with respect to their regenerative effects after transplantation, both their cellular identity and the regulating factors involved have remained vague. The aim of this article is to define OEC and Schwann-cell identity in molecular terms, and to discuss crucial factors that are involved in determination in vitro and in vivo. Distinct OEC features such as the down-regulation of the low affinity neurotrophin receptor p75NTR by neuronal contact are apparent in vivo under physiological conditions, whereas OECs acquire a Schwann cell-like phenotype and up-regulate p75NTR expression in vitro and following transplantation into the lesioned spinal cord. This might indicate that establishment of the OEC phenotype depends on specific axonal stimuli. In this review we hypothesize that OECs and Schwann cells possess malleable cellular phenotypes that acquire distinct features only upon specific interaction with their natural neuronal partner. This concept is consistent with previous findings in vitro and in vivo, and might be relevant for studies that use OECs and Schwann cells for nervous system repair.

scholarly journals Calcitonin gene-related peptide promotes Schwann cell proliferation.

1995 ◽  
Vol 129 (3) ◽  
pp. 789-796 ◽  
Author(s):  
L Cheng ◽  
M Khan ◽  
A W Mudge
Keyword(s):  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Neutral Endopeptidase ◽  
Calcitonin Gene Related Peptide ◽  
Intracellular Camp ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Glial Growth Factor

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. EMBO (Eur. Mol. Biol. Organ.) J. 9:915-920. Neuropeptides and beta-adrenergic agonists have been reported to have no effect on potentiating the mitogenic response of either PDGF or GGF. 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 PDGF.

Acetylcholine inhibits cell cycle progression in rat Schwann cells by activation of the M2 receptor subtype

2007 ◽  
Vol 3 (4) ◽  
pp. 269-279 ◽  
Author(s):  
Simona Loreti ◽  
Ruggero Ricordy ◽  
M. Egle De Stefano ◽  
Gabriella Augusti-Tocco ◽  
Ada Maria Tata
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Cell Cycle Progression ◽  
Receptor Activation ◽  
Neonatal Rat ◽  
Receptor Subtype ◽  
Cell Nuclei

AbstractCultures of Schwann cells from neonatal rat sciatic nerves were treated with acetylcholine agonists and the effects on cell proliferation evaluated. 3[H]-thymidine incorporation shows that acetylcholine (ACh) receptor agonists inhibit cell proliferation, and FACS analysis demonstrates cell-cycle arrest and accumulation of cells in the G1 phase. The use of arecaidine, a selective agonist of muscarinic M2 receptors reveals that this effect depends mainly on M2 receptor activation. The arecaidine dependent-block in G1 is reversible because removal of arecaidine from the culture medium induces progression to the S phase. The block of the G1-S transition is also characterized by modulation of the expression of several cell-cycle markers. Moreover, treatment with ACh receptor agonist causes both a decrease in the PCNA protein levels in Schwann cell nuclei and an increase in p27 and p53 proteins. Finally, immuno-electron microscopy demonstrates that M2 receptors are expressed by Schwann cells in vivo. These results indicate that ACh, by modulating Schwann cell proliferation through M2 receptor activation, might contribute to their progression to a more differentiated phenotype.

scholarly journals Immunoreactive myelin basic proteins are not detected when shiverer mutant Schwann cells and fibroblasts are co-cultured with normal neurons.

1984 ◽  
Vol 98 (4) ◽  
pp. 1291-1295 ◽  
Author(s):  
H D Shine ◽  
R L Sidman
Keyword(s):  
Nervous System ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Genetic Locus ◽  
Neuronal Cells ◽  
Recessive Mutation ◽  
Basic Proteins ◽  
Cellular Target

Shiverer (shi) is an autosomal recessive mutation in mice that results in hypomyelination in the central nervous system (CNS) but normal myelination in the peripheral nervous system (PNS). Myelin basic proteins (MBPs) are virtually absent in both PNS and CNS. It is not known whether the cellular target in the PNS is the myelin-forming Schwann cell or another cell type which secondarily affects the Schwann cell. To determine the cellular target of the shi gene, we have adapted tissue culture techniques that allow co-culture of pure populations of mouse sensory neurons of one genotype with Schwann cells and fibroblasts of another genotype under conditions that permit myelin formation. These cultures were stained immunocytochemically as whole mounts to determine whether MBPs were expressed under various in vitro conditions. In single-genotype cultures, presence or absence of MBPs was consistent with earlier in vivo results: +/+ cultures were MBP-positive and shi/shi cultures were MBP-negative. In mixed-genotype cultures, visualization of MBPs in myelin accorded with the genotype of the non-neuronal Schwann cells and fibroblasts and not with the neurons--those cultures that contained +/+ non-neuronal cells were MBP-positive and those with shi/shi non-neuronal cells were MBP-negative, independent of the neuronal genotype. These results rule out neurons or circulating substances as mediators of the influence of the shi genetic locus on MBP synthesis and deposition in peripheral myelin.

scholarly journals Studies on cultured Schwann cells: the induction of myelin synthesis, and the control of their proliferation by a new growth factor

1981 ◽  
Vol 95 (1) ◽  
pp. 215-230
Author(s):  
J. P. Brockes ◽  
K. J. Fryxell ◽  
G. E. Lemke
Keyword(s):  
Molecular Weight ◽  
Growth Factor ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Solid Phase ◽  
Immunological Methods ◽  
Subunit Molecular Weight ◽  
Cultured Schwann Cells

We have recently described the use of immunological methods to identify and purify rat Schwann cells. In dissociated cultures of neonatal sciatic nerve, all of the cells can be identified by antigenic criteria as either Schwann cells or fibroblasts. The fibroblasts may be removed by treatment with antiserum to the Thy-1 antigen and complement. The purified Schwann cells have been used to study the regulation of the expression of myelin components, and the stimulation of Schwann cell division by a soluble growth factor. Among the components of myelin, we have concentrated on the peripheral myelin glycoprotein P0, which constitutes 50–60% of the protein in peripheral myelin. We have studied the distribution of P0 in vitro and in vivo by immunofluorescence, immuno-autoradiography on SDS gels, and solid-phase radioimmunoassay. Our results support the hypothesis that P0 is induced specifically as a consequence of the interaction between the Schwann cell and the myelinated type of axon. The level of P0 in the myelin membrane is at least 1000-fold higher than in the Schwann cell membrane. Purified Schwann cells divide very slowly in a conventional tissue culture medium. This has allowed us to purify a new growth factor from extracts of brain and pituitary, tentatively named Glial Growth Factor (GGF). The activity resides in a basic protein with a native molecular weight of 6 × 10(4) daltons and a subunit molecular weight of 3 × 10(4) daltons, which is active at levels comparable to those of epidermal growth factor. GGF is mitogenic for Schwann cells, astrocytes and muscle fibroblasts.

scholarly journals Axonal regulation of Schwann cell integrin expression suggests a role for alpha 6 beta 4 in myelination.

1993 ◽  
Vol 123 (5) ◽  
pp. 1223-1236 ◽  
Author(s):  
S Einheber ◽  
T A Milner ◽  
F Giancotti ◽  
J L Salzer
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Basal Lamina ◽  
Cell Contact ◽  
Myelin Associated Glycoprotein ◽  
Dorsal Root Ganglia Neurons ◽  
Outer Plasma Membrane

Ensheathment and myelination of axons by Schwann cells in the peripheral nervous system requires contact with a basal lamina. The molecular mechanism(s) by which the basal lamina promotes myelination is not known but is likely to reflect the activity of integrins expressed by Schwann cells. To initiate studies on the role of integrins during myelination, we characterized the expression of two integrin subunits, beta 1 and beta 4, in an in vitro myelination system and compared their expression to that of the glial adhesion molecule, the myelin-associated glycoprotein (MAG). In the absence of neurons, Schwann cells express significant levels of beta 1 but virtually no beta 4 or MAG. When Schwann cells are cocultured with dorsal root ganglia neurons under conditions promoting myelination, expression of beta 4 and MAG increased dramatically in myelinating cells, whereas beta 1 levels remained essentially unchanged. (In general agreement with these findings, during peripheral nerve development in vivo, beta 4 levels also increase during the period of myelination in sharp contrast to beta 1 levels which show a striking decrease.) In cocultures of neurons and Schwann cells, beta 4 and MAG appear to colocalize in nascent myelin sheaths but have distinct distributions in mature sheaths, with beta 4 concentrated in the outer plasma membrane of the Schwann cell and MAG localized to the inner (periaxonal) membrane. Surprisingly, beta 4 is also present at high levels with MAG in Schmidt-Lanterman incisures. Immunoprecipitation studies demonstrated that primary Schwann cells express beta 1 in association with the alpha 1 and alpha 6 subunits, while myelinating Schwann cells express alpha 6 beta 4 and possibly alpha 1 beta 1. beta 4 is also downregulated during Wallerian degeneration in vitro, indicating that its expression requires continuous Schwann cell contact with the axon. These results indicate that axonal contact induces the expression of beta 4 during Schwann cell myelination and suggest that alpha 6 beta 4 is an important mediator of the interactions of myelinating Schwann cells with the basal lamina.

scholarly journals Developmental changes in myelin-induced proliferation of cultured Schwann cells.

1987 ◽  
Vol 104 (3) ◽  
pp. 655-660 ◽  
Author(s):  
J E Yoshino ◽  
P W Mason ◽  
G H DeVries
Keyword(s):  
Cell Proliferation ◽  
Schwann Cell ◽  
Myelin Basic Protein ◽  
Schwann Cells ◽  
Basic Protein ◽  
Small Population ◽  
Developmental Changes ◽  
Cultured Schwann Cells

Schwann cell proliferation induced by a myelin-enriched fraction was examined in vitro. Although nearly all the Schwann cells contained material that was recognized by antisera to myelin basic protein after 24 h, only 1% of the cells were synthesizing DNA. 72 h after the addition of the mitogen a maximum of 10% of the cells incorporated [3H]thymidine. If the cultures were treated with the myelin-enriched fraction for 24 h and then washed, the number of proliferating Schwann cells decreased by 75% when compared with those cells that were incubated with the mitogen continuously. When Schwann cells were labeled with [14C]thymidine followed by a pulse of [3H]thymidine 24 h later, every Schwann cell labeled with [3H]thymidine was also labeled with [14C]thymidine. Although almost every Schwann cell can metabolize the myelin membranes within 24 h of exposure, a small population of cell initially utilizes the myelin as a mitogen, and this population continues to divide only if myelin is present in the extracellular media. The percentage of the Schwann cells that initially recognize the myelin-enriched fraction as a mitogen is dependent upon the age of the animal from which the cells were prepared.

scholarly journals Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jia-Huang Liu ◽  
Qi-Fei Wu ◽  
Jun-Ke Fu ◽  
Xiang-Ming Che ◽  
Hai-Jun Li
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Nude Mice ◽  
Serum Glucose ◽  
Migration And Invasion ◽  
Endocrine Effect

Obesity could increase the risk of esophageal squamous cell carcinoma (ESCC) and affect its growth and progression, but the mechanical links are unclear. The objective of the study was to explore the impact of obesity on ESCC growth and progression utilizing in vivo trials and cell experiments in vitro. Diet-induced obese and lean nude mice were inoculated with TE-1 cells, then studied for 4 weeks. Serum glucose, insulin, leptin, and visfatin levels were assayed. Sera of nude mice were obtained and then utilized to culture TE-1. MTT, migration and invasion assays, RT-PCR, and Western blotting were used to analyze endocrine effect of obesity on cell proliferation, migration, invasion, and related genes expression of TE-1. Obese nude mice bore larger tumor xenografts than lean animals, and were hyperglycemic and hyperinsulinemic with an elevated level of leptin and visfatin in sera, and also were accompanied by a fatty liver. As for the subcutaneous tumor xenograft model, tumors were more aggressive in obese nude mice than lean animals. Tumor weight correlated positively with mouse body weight, liver weight of mice, serum glucose, HOMA-IR, leptin, and visfatin. Obesity prompted significant TE-1 cell proliferation, migration, and invasion by endocrine mechanisms and impacted target genes. The expression of AMPK and p-AMPK protein decreased significantly ( P < 0.05 ); MMP9, total YAP, p-YAP, and nonphosphorylated YAP protein increased significantly ( P < 0.05 ) in the cells cultured with conditioned media and xenograft tumor from the obese group; the mRNA expression of AMPK decreased significantly ( P < 0.05 ); YAP and MMP9 mRNA expression increased significantly ( P < 0.05 ) in the cells exposed to conditioned media from the obese group. In conclusion, the altered adipokine milieu and metabolites in the context of obesity may promote ESCC growth in vivo; affect proliferation, migration, and invasion of ESCC cells in vitro; and regulate MMP9 and AMPK-YAP signaling pathway through complex effects including the endocrine effect.

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