Heparin potentiates the action of plasma membrane‐associated growth stimulatory activity

Nagasaki, Takayuki; Lieberman, M. A.

doi:10.1002/jcp.1041330222

Cited by 12 publications

(8 citation statements)

References 42 publications

(43 reference statements)

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“…Gel-purified mitogen, which is highly mitogenic for Schwann cells and oligodendrocytes, had no effect on the proliferation of NR6-3T3 fibroblasts, GFAPt astrocytes, or OX42+ microglia. The inability of the mitogen to stimulate NR6-3T3 cells, which proliferate vigorously in response to acidic and basic FGF (Nagasaki and Lieberman, 1987), clearly distinguishes the mitogen from previously described FGFs. This result corroborates our previous data showing that antibodies that recognize and immunoprecipitate bFGF are unable to deplete activity from mitogenic extracts (Ratner et al, 1988).…”

Section: Gel-purified Mitogen Stimulates the Proliferation Of Cells Omentioning

confidence: 90%

Schwann cells and cells in the oligodendrocyte lineage proliferate in response to a 50,000 dalton membrane‐associated mitogen present in developing brain

Nordlund

Hong

Fei

et al. 1992

Glia

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The neuronal cell surface is believed to carry a mitogenic signal for peripheral glial cells. We have purified a mitogen from fetal bovine brain membranes that, in common with the PNS neuronal mitogen, stimulates the proliferation of Schwann cells in vitro and binds heparin. The purified mitogen has an apparent molecular weight of 50,000 daltons as estimated by elution of activity from non-reducing polyacrylamide gels. Since the developing central nervous system is a rich source of mitogen, we tested whether the protein is mitogenic for one or more cell types isolated from the developing brain. Purified mitogen was added to enriched cultures of astrocytes or developing oligodendrocytes, or to microglial cells. The analyses demonstrated that the protein is mitogenic for developing oligodendrocytes but not astrocytes or microglial cells. These results suggest that during development a membrane-associated mitogen present in the brain might regulate the proliferation of developing oligodendrocytes, and consequently, the population size of oligodendrocytes in the brain.

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Section: Gel-purified Mitogen Stimulates the Proliferation Of Cells Omentioning

confidence: 90%

Schwann cells and cells in the oligodendrocyte lineage proliferate in response to a 50,000 dalton membrane‐associated mitogen present in developing brain

Nordlund

Hong

Fei

et al. 1992

Glia

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“…On the one hand, heparin has been shown to restore the biological activity of old preparations of aFGF and bFGF [14], to protect aFGFs from proteolysis [23,29] and heat inactivation [14] and to prolong its biological half-life [3]. On the other hand, it has been shown that heparin potentiates the action of plasma membrane-associated growth stimulatory activity [24] and modulates the binding of bFGF to bovine brain membranes since this binding is reduced by 75°70 after heparinase treatment [4]. In our experiments, aFGF alone stimulated the proliferation of sparsely seeded EC and retained the same activity throughout the lesion repair experiments (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Behavior of confluent endothelial cells after irradiation. Modulation of wound repair by heparin and acidic fibroblast growth factor

Klein-Soyer

Beretz

Cazenave

et al. 1990

Biology of the Cell

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Image analysis was used to study the repair process of a circular mechanical lesion of confluent human endothelial cells in culture after irradiation (10 Gy) prior to wounding. Coverage of denuded areas 48 and 96 h after injury of endothelial cells was identical in control and irradiated cultures, although the labeling index was lowered by 80 to 95% in irradiated cultures. The cell density of non damaged irradiated areas was decreased by 50%. When cultures were submitted to increasing doses of radiation (5.0-30 Gy), the labeling index of the cells diminished rapidly between 0 and 5.0 Gy and reached a plateau at 10 Gy. The decrease in cell density (50% of control at 96 h) was identical at each dose of radiation. Thus cell migration alone could be sufficient for the repair of the lesion, while cell proliferation would mainly maintain the original cell density. The addition of heparin to the culture medium slowed down cell migration and proliferation, but the speed of repair was identical in irradiated and non-irradiated cultures. Acidic fibroblast growth factor plus heparin accelerated equally the repair process whether the cultures were irradiated or not. In irradiated cultures the presence of acidic fibroblast growth factor and heparin maintained cell density in confluent areas at a level similar to that in non-irradiated damaged control cultures without addition of mitogens. Thus heparin and acidic fibroblast growth factor play a role in cell proliferation, in the maintenance of the cell monolayer integrity and in restoring a continuous layer by rapid cell migration and elongation after irradiation.

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“…NR6 cells, an epidermal growth factor receptor-negative variant of Swiss 3T3 cells (14), were used to assay mitogenicity of FGF as described (15).…”

mentioning

confidence: 99%

The neuronal cell-surface molecule mitogenic for Schwann cells is a heparin-binding protein.

Ratner

Hong

Lieberman

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

115

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The cell surface of embryonic peripheral neurons provides a mitogenic stimulus for Schwann cells. We report (a) the solubilization of this mitogenic activity from rat dorsal root ganglion neurons grown in tissue culture and (u) the solubilization and partial purification of mitogenic activity from neonatal rat brains. Extracted mitogenic activity is peripheral rather than intrinsic to the membrane, stable after extraction, and active as a mitogen in the absence of serum (the most tringent criterion defning the neuronal mitogen). We have previously provided evidence suggesting that a neuronal cellsurface heparan sulfate proteoglycan is required for expression of the neurons' mitogenic activity. We now show that mitogenic activity can be extracted from the membrane diociated from proteoglycan as assayed by its ability to bind to immobilized heparin. After dissociation, low concentrations of heparin (1 Fg/ml) inhibit the ability of the mitogen to stimulate Schwann cell division. Basic fibroblast growth factor (FGF) is weakly mitogenic for Schwann cells, but it is not present in mitogenic brain extracts (based on immunoblottig. Immunodepletion experiments with specific antibodies to FGF indicate that the mitogenic activity extracted from neurons is not a form of this heparin-binding mitogen. Acidic FGF is not mitogenic for Schwann cells and is not present in mitogenic brain extracts. We suggest that these and previous data indicate the neurite mitogen is a proteoglycan-growth factor complex that limits mitogenic activity to the axonal surface, protects mitogen against inactivation by other proteoglycans, and provides for effective presentation of mitogen to the Schwann cell.A complex series of cell-cell interactions among neurons, Schwann cells, and fibroblasts lead to the formation of the peripheral nerve. One of these interactions is the neuronstimulated proliferation of Schwann cells, first suggested by experiments in which the ratio of Schwann cells to neurons remained constant when neuronal numbers were altered (1). These in vivo observations have been extended in an in vitro system is which neurons and Schwann cells can be separated and recombined; in vitro studies demonstrate that contact with the neuronal surface causes Schwann cells to undergo a dramatic increase in both DNA synthesis and cell division (2-4). Several lines of evidence indicate that the cell surface of the neuron (rather than a released factor) carries the mitogenic stimulus. Membrane fragments from dorsal root ganglion neurons grown in tissue culture mimic the mitogenicity of whole cells, and trypsin treatment of intact neurons in culture prevents the mitogenic response of Schwann cells added to these neurons (5). Furthermore, a semipermeable collagen membrane interposed between Schwann cells and neurons in the culture dish inhibits the mitogenic response (6), and conditioned medium from neurons is not mitogenic for Schwann cells (2, 4).Recent tissue culture studies indicate that the neuronal cell-surface mitogen is associated coval...

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Heparin potentiates the action of plasma membrane‐associated growth stimulatory activity

Cited by 12 publications

References 42 publications

Schwann cells and cells in the oligodendrocyte lineage proliferate in response to a 50,000 dalton membrane‐associated mitogen present in developing brain

Schwann cells and cells in the oligodendrocyte lineage proliferate in response to a 50,000 dalton membrane‐associated mitogen present in developing brain

Behavior of confluent endothelial cells after irradiation. Modulation of wound repair by heparin and acidic fibroblast growth factor

The neuronal cell-surface molecule mitogenic for Schwann cells is a heparin-binding protein.

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