Lysophosphatidic acid stimulates actomyosin contraction in astrocytes

Manning, Timothy J.; Rosenfeld, Steven S.; Sontheimer, Harald

doi:10.1002/(sici)1097-4547(19980801)53:3<343::aid-jnr8>3.0.co;2-a

Cited by 55 publications

(39 citation statements)

References 47 publications

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“…The fivefold greater lesion size that we observed 2 weeks after ablation of reactive astrocytes and SCI is greater than might be expected solely on the basis of induced and secondary cell loss and suggests that loss of reactive astrocytes contributed to failure of wound contraction. This finding supports evidence that astrocytes have receptor-regulated contractile properties likely to be involved in wound healing (Manning et al, 1998).…”

Section: Specificity Of the Transgenic Modelsupporting

confidence: 87%

Reactive Astrocytes Protect Tissue and Preserve Function after Spinal Cord Injury

Faulkner¹,

Herrmann²,

Woo³

et al. 2004

J. Neurosci.

1,374

1,097

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Reactive astrocytes are prominent in the cellular response to spinal cord injury (SCI), but their roles are not well understood. We used a transgenic mouse model to study the consequences of selective and conditional ablation of reactive astrocytes after stab or crush SCI. Mice expressing a glial fibrillary acid protein-herpes simplex virus-thymidine kinase transgene were given mild or moderate SCI and treated with the antiviral agent ganciclovir (GCV) to ablate dividing, reactive, transgene-expressing astrocytes in the immediate vicinity of the SCI. Small stab injuries in control mice caused little tissue disruption, little demyelination, no obvious neuronal death, and mild, reversible functional impairments. Equivalent small stab injuries in transgenic mice given GCV to ablate reactive astrocytes caused failure of blood-brain barrier repair, leukocyte infiltration, local tissue disruption, severe demyelination, neuronal and oligodendrocyte death, and pronounced motor deficits. Moderate crush injuries in control mice caused focal tissue disruption and cellular degeneration, with moderate, primarily reversible motor impairments. Equivalent moderate crush injuries combined with ablation of reactive astrocytes caused widespread tissue disruption, pronounced cellular degeneration, and failure of wound contraction, with severe persisting motor deficits. These findings show that reactive astrocytes provide essential activities that protect tissue and preserve function after mild or moderate SCI. In nontransgenic animals, crush or contusion SCIs routinely exhibit regions of degenerated tissue that are devoid of astrocytes. Our findings suggest that identifying ways to preserve reactive astrocytes, to augment their protective functions, or both, may lead to novel approaches to reducing secondary tissue degeneration and improving functional outcome after SCI.

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Section: Specificity Of the Transgenic Modelsupporting

confidence: 87%

Reactive Astrocytes Protect Tissue and Preserve Function after Spinal Cord Injury

Faulkner¹,

Herrmann²,

Woo³

et al. 2004

J. Neurosci.

1,374

1,097

View full text Add to dashboard Cite

show abstract

“…To ensure that myosin II was being inhibited we looked for the effect of drug or RNAi on cell morphology and on cytokinesis, because both depend on myosin II function. Both types of treatment produced morphological changes similar to previous descriptions (Supplemental Figure 3), with formation of multiple long, branched cytoplasmic processes (Manning et al, 1998(Manning et al, , 2000. Furthermore, both drug and RNAi treatment produced obvious defects in cytokinesis (Supplemental Figure 4).…”

Section: Glioma Migration On a Two-dimensional Surface Resembles How supporting

confidence: 80%

The Role of Myosin II in Glioma Invasion of the Brain

Beadle

Assanah

Monzo

et al. 2008

MBoC

Self Cite

292

334

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The ability of gliomas to invade the brain limits the efficacy of standard therapies. In this study, we have examined glioma migration in living brain tissue by using two novel in vivo model systems. Within the brain, glioma cells migrate like nontransformed, neural progenitor cells-extending a prominent leading cytoplasmic process followed by a burst of forward movement by the cell body that requires myosin II. In contrast, on a two-dimensional surface, glioma cells migrate more like fibroblasts, and they do not require myosin II to move. To explain this phenomenon, we studied glioma migration through a series of synthetic membranes with defined pore sizes. Our results demonstrate that the A and B isoforms of myosin II are specifically required when a glioma cell has to squeeze through pores smaller than its nuclear diameter. They support a model in which the neural progenitor-like mode of glioma invasion and the requirement for myosin II represent an adaptation needed to move within the brain, which has a submicrometer effective pore size. Furthermore, the absolute requirement for myosin II in brain invasion underscores the importance of this molecular motor as a potential target for new anti-invasive therapies to treat malignant brain tumors. INTRODUCTIONMalignant gliomas are a group of primary brain tumors that have remained resistant to therapy and that have a dismal prognosis (Buckner et al., 2007;Stupp et al., 2007). Part of the reason for this state of affairs is that although gliomas rarely metastasize outside the CNS, they are capable of spreading long distances within the brain (Sherer, 1940;Burger and Kleihues, 1989;Hoelzinger et al., 2007). This invasive behavior limits the effectiveness of local therapies and contributes to the high mortality rate seen in these tumors (Lim et al., 2007). Preventing glioma invasion therefore has the potential to convert this highly malignant tumor into a focal disease, which could then be effectively treated with focal therapies, such as radiation and surgery. Realizing this outcome, however, will require a detailed understanding how gliomas invade normal brain.Gliomas typically invade the brain by migrating long distances through white matter tracts and by infiltrating cortex and subcortical gray matter structures. Brain parenchyma (neuropil) is composed of tightly packed neuronal and glial processes, and it is characterized by extracellular spaces that are in the submicrometer range (Thorne and Nicholson, 2006). This environment therefore represents a particular mechanical challenge to motile cells, such as gliomas, that need to insinuate themselves through a highly constraining brain matrix to migrate. Unfortunately, there is very little information about how glioma cells accomplish this process in vivo. Some insight is provided by studies of embryonic and early postnatal brain, where neural progenitor cells migrate along radial glial cells, and to some extent through the white matter and cortex before stopping and differentiating into mature neurons and glia. Ti...

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“…We performed similar experiments using silicone as a substrate, 21,24 (Figures 4G through 4L), with similar results. Treatment of the Monc-1 cells with carbachol did not lead to cell death as determined by trypan blue exclusion assays before and after treatment (data not shown).…”

Section: Resultssupporting

confidence: 56%

Transforming Growth Factor-β-Induced Differentiation of Smooth Muscle From a Neural Crest Stem Cell Line

Chen

Lechleider

2004

Circulation Research

165

124

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Abstract-During vascular development, nascent endothelial networks are invested with a layer of supporting cells called pericytes in capillaries or smooth muscle in larger vessels. The cellular lineage of smooth muscle precursors and factors responsible for regulating their differentiation remain uncertain. In vivo, cells derived from the multipotent neural crest can give rise to vascular smooth muscle in parts of the head and also the cardiac outflow tract. Although transforming growth factor-␤ (TGF-␤) has previously been shown to induce some smooth muscle markers from primary cultures of neural crest stem cells, the extent of the differentiation induced was not clear. In this study, we demonstrate that TGF-␤ can induce many of the markers and characteristics of vascular smooth muscle from a neural crest stem cell line, Monc-1. Within 3 days of in vitro treatment, TGF-␤ induces multiple smooth muscle-specific markers, while downregulating epithelial markers present on the parent cells. Treatment with TGF-␤ also induces a contractile phenotype that responds to the muscarinic agonist carbachol and is not immediately reversed on TGF-␤ withdrawal. Examination of the signaling pathways involved revealed that TGF-␤ activation of Smad2 and Smad3 appear to be essential for the observed differentiation. Taken together, this system provides a novel model of smooth muscle differentiation that reliably recapitulates the process observed in vivo and allows for dissection of the pathways and processes involved in this process.

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Lysophosphatidic acid stimulates actomyosin contraction in astrocytes

Cited by 55 publications

References 47 publications

Reactive Astrocytes Protect Tissue and Preserve Function after Spinal Cord Injury

Reactive Astrocytes Protect Tissue and Preserve Function after Spinal Cord Injury

The Role of Myosin II in Glioma Invasion of the Brain

Transforming Growth Factor-β-Induced Differentiation of Smooth Muscle From a Neural Crest Stem Cell Line

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