Effects of transforming growth factor‐β1 on the extracellular matrix and cytoskeleton of cultured astrocytes

Baghdassarian, Denise; Toru-Delbauffe, D.; Gavaret, Jean‐Michel; Martineau, Pierre

doi:10.1002/glia.440070302

Cited by 87 publications

(61 citation statements)

References 54 publications

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“…TGF-␤s have been shown to elicit profound effects on the actin cytoskeleton and stress fibers, enhance the expression of GFAP, and inhibit the proliferation in cultured cerebellar astrocytes (63)(64)(65). The Smad4…”

Section: Discussionmentioning

confidence: 99%

Cerebellar Deficits and Hyperactivity in Mice Lacking Smad4

Zhou

Zhao

et al. 2003

Journal of Biological Chemistry

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Smad4 is a central mediator of TGF-␤ signals, which are known to play essential roles in many biological processes. Using a Cre-loxP approach to overcome early embryonic lethality, we have studied functions of TGF-␤/Smad4 signals in the central nervous system (CNS). No obvious deficits were detected in mice carrying the targeted disruption of Smad4 in the CNS. The overall morphology of the hippocampus appeared normal. There was no change in the proliferation of neuronal precursor cells, nor in several forms of synaptic plasticity. In contrast, deletion of Smad4 resulted in a marked decrease in the number of cerebellar Purkinje cells and parvalbumin-positive interneurons. Accompanied by the abnormality in the cerebellum, mutant mice also exhibited significantly increased vertical activity. Thus, our study reveals an unexpected role for Smad4 in cerebellar development and in the control of motor function.

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Section: Discussionmentioning

confidence: 99%

Cerebellar Deficits and Hyperactivity in Mice Lacking Smad4

Zhou

Zhao

et al. 2003

Journal of Biological Chemistry

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“…Thus, our results may suggest (1) that the high content of fibronectin (as found in VimϪ/Ϫ astrocytes) is not per se permissive in the absence of other potential growth molecules or (2) that punctuate aggregates of fibronectin (as found in double KO and GFAPϪ/Ϫ astrocytes) are more effective in forming complexes with other permissive ECM molecules. Reorganizations in the GFAP network have indeed been correlated with modifications of the ECM (Baghdassarian et al, 1993;Trentin and Moura-Neto, 1995).…”

Section: Is the Absence Of Gfap Associated With Modifications In The mentioning

confidence: 99%

Inactivation of the Glial Fibrillary Acidic Protein Gene, But Not That of Vimentin, Improves Neuronal Survival and Neurite Growth by Modifying Adhesion Molecule Expression

et al. 2001

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Intermediate filaments (IFs) are a major component of the cytoskeleton in astrocytes. Their role is far from being completely understood. Immature astrocytes play a major role in neuronal migration and neuritogenesis, and their IFs are mainly composed of vimentin. In mature differentiated astrocytes, vimentin is replaced by the IF protein glial fibrillary acidic protein (GFAP). In response to injury of the CNS in the adult, astrocytes become reactive, upregulate the expression of GFAP, and reexpress vimentin. These modifications contribute to the formation of a glial scar that is obstructive to axonal regeneration. Nevertheless, astrocytes in vitro are considered to be the ideal substratum for the growth of embryonic CNS axons. In the present study, we have examined the potential role of these two major IF proteins in both neuronal survival and neurite growth. For this purpose, we cocultured wild-type neurons on astrocytes from three types of knock-out (KO) mice for GFAP or/and vimentin in a neuron-astrocyte coculture model. We show that the double KO astrocytes present many features of immaturity and greatly improve survival and neurite growth of cocultured neurons by increasing cell-cell contact and secreting diffusible factors. Moreover, our data suggest that the absence of vimentin is not a key element in the permissivity of the mutant astrocytes. Finally, we show that only the absence of GFAP is associated with an increased expression of some extracellular matrix and adhesion molecules. To conclude, our results suggest that GFAP expression is able to modulate key biochemical properties of astrocytes that are implicated in their permissivity.

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“…TGF-β1 has been suggested to be neuroprotective via stimulation of astrocytic genes (Buisson et al, 1998). Additionally, TGF-β1 stimulates the expression ECM molecules that promote wound healing (Baghdassarian et al, 1993;Zambruno et al, 1995) and that regulate neurite outgrowth (Asher et al, 2000;Smith and Hale, 1997), indicating that the astrocytic response to this cytokine is significant following CNS injury.…”

Section: Tgf-β1 In Cns Injurymentioning

confidence: 99%

Increased adenine nucleotide translocator 1 in reactive astrocytes facilitates glutamate transport

Buck¹,

Jurynec

et al. 2003

Experimental Neurology

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A hallmark of central nervous system (CNS) pathology is reactive astrocyte production of the chronic glial scar that is inhibitory to neuronal regeneration. The reactive astrocyte response is complex; these cells also produce neurotrophic factors and are responsible for removal of extracellular glutamate, the excitatory neurotransmitter that rises to neurotoxic levels in injury and disease. To identify genes expressed by reactive astrocytes, we employed an in vivo model of the glial scar and differential display PCR and found an increase in the level of Ant1, a mitochondrial ATP/ADP exchanger that facilitates the flux of ATP out of the mitochondria. Ant1 expression in reactive astrocytes is regulated by transforming growth factor-β1, a pluripotent CNS injury-induced cytokine. The significance of increased Ant1 is evident from the observation that glutamate uptake is significantly decreased in astrocytes from Ant1 null mutant mice while a specific Ant inhibitor reduces glutamate uptake in wild-type astrocytes. Thus, the astrocytic response to CNS injury includes an apparent increase in energy mobilization capacity by Ant1 that contributes to neuroprotective, energy-dependent glutamate uptake.

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Effects of transforming growth factor‐β1 on the extracellular matrix and cytoskeleton of cultured astrocytes

Cited by 87 publications

References 54 publications

Cerebellar Deficits and Hyperactivity in Mice Lacking Smad4

Cerebellar Deficits and Hyperactivity in Mice Lacking Smad4

Inactivation of the Glial Fibrillary Acidic Protein Gene, But Not That of Vimentin, Improves Neuronal Survival and Neurite Growth by Modifying Adhesion Molecule Expression

Increased adenine nucleotide translocator 1 in reactive astrocytes facilitates glutamate transport

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