Vitronectin overrides a negative effect of TNF-alpha on astrocyte migration.

Faber-Elman, A; Lavie, Vered; Schvartz, Iris; Shaltiel, Shmuel; Schwartz, Michal

doi:10.1096/fasebj.9.15.8529840

Cited by 35 publications

(22 citation statements)

References 3 publications

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“…GFAP mRNA and GFAP protein levels are increased a few hours and a few days postlesion, respectively (Mucke et al, 1991). Similar changes were obtained in purified astrocytic cultures by Yu et al (1993), Ghirnikar et al (1994), andFaber-Elman et al (1995), who induced astrogliosis by mechanical lesion of the cells. We have taken advantage of the possibility of culturing dissociated neurons on an astroglial monolayer (Noble et al, 1984;Hatten, 1985) to reproduce more completely the phenomena induced by an in vivo lesion, in particular, the presence in the same place of cut ends of both axons and glial processes.…”

Section: An In Vitro Model For Cns Injurysupporting

confidence: 78%

Neuritic Outgrowth Associated with Astroglial Phenotypic Changes Induced by Antisense Glial Fibrillary Acidic Protein (GFAP) mRNA in Injured Neuron–Astrocyte Cocultures

et al. 1997

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In the adult CNS, axons fail to regenerate after injury. Among the cell interactions that lead to this failure are those developed with astrocytes. In an effort to elucidate the mechanisms underlying these negative interactions, we have used astrocytes treated with antisense glial fibrillary acidic protein (GFAP) mRNA to inhibit the formation of gliofilaments, indispensable for the astroglial morphological response to injury, and have studied their permissivity for neuritic outgrowth. In a neuronastrocyte coculture, a mechanical lesion led to hypertrophy of astrocytes neighboring the lesion. Neuronal cell bodies and neurites were absent both from the area of lesion and from its surroundings. Reactive astrocytes appeared, therefore, to be a nonpermissive substrate. Transfection that used antisense GFAP mRNA blocked astroglial morphological changes and was characterized by both a persistence of neuronal cell bodies in the vicinity of the lesion site and a growth of neurites into the same region. These morphological differences were associated with a 46% decrease in the GFAP translation capacity and a 50% increase in the concentration of GAP-43 in the treated cultures. Neurons were associated mainly with an extracellular laminin network, which was predominant at the lesion site in treated cocultures. In contrast, those astrocytes highly lamininimmunoreactive appeared to be a nonpermissive substrate for neurons. These results show that inhibition in GFAP synthesis, leading to a reduction of astroglial hypertrophy, relieves the blockade of neuritic outgrowth that normally is observed after a lesion. The mechanisms may involve changes in the secretion of extracellular matrix molecules by astrocytes.

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Section: An In Vitro Model For Cns Injurysupporting

confidence: 78%

Neuritic Outgrowth Associated with Astroglial Phenotypic Changes Induced by Antisense Glial Fibrillary Acidic Protein (GFAP) mRNA in Injured Neuron–Astrocyte Cocultures

et al. 1997

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“…Other cytokines appear to inhibit astrocyte migration and may act in combination with migrationinducing signals. For example, in vitro TNF-· blocks astrocyte migration [Faber-Elman et al, 1995] and while this inhibition was not reversed by TGF-ß, laminin or fibronectin, it was reversed by the addition of vitronectin [Faber-Elman et al, 1995]. Whether any of these signals regulate astrocyte migration through the intact CNS remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Control of Astrocyte Migration in the Developing Cerebral Cortex

Jacobsen

Miller

2003

Dev Neurosci

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Development of the vertebrate central nervous system is characterized by significant long distance cell migration. While the radial migration of neuronal precursors to their final location is well established the migration of glial cells and their precursors is less well understood. To define the pathways of migration and dissect the cell and molecular mechanisms mediating such migration requires the development of appropriate models. Here we show that purified neonatal astrocytes injected into organotypic slice cultures of developing cerebral cortex migrate in defined patterns depending on where they are placed within the tissue. Injection into gray matter resulted in radially oriented migration either towards the pial or ventricular surface. By contrast injection into developing white matter resulted in largely longitudinal migration along developing axon tracts. While the cytoarchitecture of the tissue influenced the pattern of migration, the extent of migration appeared to be regulated primarily by the age of the host tissue. Homochronic injections performed prior to postnatal day 4 resulted in extensive migration while after day 7 migration was relatively limited. Heterochronic injections indicated that while astrocytes within the 1st postnatal week retained the capacity to migrate extensively, older tissue failed to support extensive migration of either young or old astrocytes. These data suggest the existence of distinct migrational cues in the CNS and that environmental, not cell intrinsic properties primarily regulate astrocyte migration through the developing cortex.

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“…Additionally, there is evidence that inflammatory cytokines IL1β and TNFα inhibit migration in WT astrocytes [24]. To determine if the TG2 −/− astrocyte deficiency in migration could be rescued with cytokines or further inhibited, we treated TG2 −/− astrocytes with 5 ng/mL TGFβ1, 10 ng/mL TNFα, or 5 ng/mL IL1β and measured migration.…”

Section: Resultsmentioning

confidence: 99%

“…Taken together, these results suggest that TG2 may be not be modulating the integrin pathway [11]. In order to further understand which signaling pathway TG2 may be working through, we activated different receptors that have been shown to be important in CNS injury (IL1β, TGFβ, TNFα), astrocytic migration (TGFβ, TNFα), and/or known TG2 signaling pathways [23,24,26,27]. Both IL1β and TGFβ are well known activators of the MAP kinase pathway [25,28].…”

Section: Discussionmentioning

confidence: 99%

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Inhibition or ablation of transglutaminase 2 impairs astrocyte migration

Monteagudo

Akbar

et al. 2017

Biochemical and Biophysical Research Communications

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Astrocytes play numerous complex roles that support and facilitate the function of neurons. Further, when there is an injury to the central nervous system (CNS) they can both facilitate or ameliorate functional recovery depending on the location and severity of the injury. When a CNS injury is relatively severe a glial scar is formed, which is primarily composed of astrocytes. The glial scar can be both beneficial, by limiting inflammation, and detrimental, by preventing neuronal projections, to functional recovery. Thus, understanding the processes and proteins that regulate astrocyte migration in response to injury is still of fundamental importance. One protein that is likely involved in astrocyte migration is transglutaminase 2 (TG2); a multifunctional protein expressed ubiquitously throughout the brain. Its functions include transamidation and GTPase activity, among others, and previous studies have implicated TG2 as a regulator of migration. Therefore, we examined the role of TG2 in primary astrocyte migration subsequent to injury. Using wild type or TG2−/− astrocytes, we manipulated the different functions and conformation of TG2 with novel irreversible inhibitors or mutant versions of the protein. Results showed that both inhibition and ablation of TG2 in primary astrocytes significantly inhibit migration. Additionally, we show that the deficiency in migration caused by deletion of TG2 can only be rescued with the native protein and not with mutants. Finally, the addition of TGFβ rescued the migration deficiency independent of TG2. Taken together, our study shows that transamidation and GTP/GDP-binding are necessary for inhibiting astrocyte migration and it is TGFβ independent.

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Vitronectin overrides a negative effect of TNF-alpha on astrocyte migration.

Cited by 35 publications

References 3 publications

Neuritic Outgrowth Associated with Astroglial Phenotypic Changes Induced by Antisense Glial Fibrillary Acidic Protein (GFAP) mRNA in Injured Neuron–Astrocyte Cocultures

Neuritic Outgrowth Associated with Astroglial Phenotypic Changes Induced by Antisense Glial Fibrillary Acidic Protein (GFAP) mRNA in Injured Neuron–Astrocyte Cocultures

Control of Astrocyte Migration in the Developing Cerebral Cortex

Inhibition or ablation of transglutaminase 2 impairs astrocyte migration

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