Smad3-dependent induction of plasminogen activator inhibitor-1 in astrocytes mediates neuroprotective activity of transforming growth factor-β1 against NMDA-induced necrosis

Fabian Docagne; Olivier Nicole; Cecilia Gabriel; Mónica Fernández-Monreal; Sylvain Lesné; Carine Ali; Laurent Plawinski; Peter Carmeliet; Eric T. MacKenzie; Alain Buisson; Denis Vivien

doi:10.1006/mcne.2002.1206

Smad3-dependent induction of plasminogen activator inhibitor-1 in astrocytes mediates neuroprotective activity of transforming growth factor-β1 against NMDA-induced necrosis

Fabian Docagne
, Olivier Nicole
, Cecilia Gabriel
, Mónica Fernández-Monreal
, Sylvain Lesné
, Carine Ali
, Laurent Plawinski
, Peter Carmeliet
, Eric T. MacKenzie
, Alain Buisson
, Denis Vivien

Neuroscience

Research output: Contribution to journal › Article › peer-review

74 Scopus citations

Abstract

The intravenous injection of the serine protease, tissue-type plasminogen activator (t-PA), has shown to benefit stroke patients by promoting early reperfusion. However, it has recently been suggested that t-PA activity, in the cerebral parenchyma, may also potentiate excitotoxic neuronal death. The present study has dealt with the role of the t-PA inhibitor, PAI-1, in the neuroprotective activity of the cytokine TGF-β1 and focused on the transduction pathway involved in this effect. We demonstrated that PAI-1, produced by astrocytes, mediates the neuroprotective activity of TGF-β1 against N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. This t-PA inhibitor, PAI-1, protected neurons against NMDA-induced neuronal death by modulating the NMDA-evoked calcium influx. Finally, we showed that the activation of the Smad3-dependent transduction pathway mediates the TGF-β-induced up-regulation of PAI-1 and subsequent neuroprotection. Overall, this study underlines the critical role of the t-PA/PAI-1 axis in the regulation of glutamatergic neurotransmission.

Original language	English (US)
Pages (from-to)	634-644
Number of pages	11
Journal	Molecular and Cellular Neuroscience
Volume	21
Issue number	4
DOIs	https://doi.org/10.1006/mcne.2002.1206
State	Published - 2002

Bibliographical note

Funding Information:
The authors were supported by grants from the CNRS and the University of Caen. The following authors received doctoral bursaries: F.D. (Regional council of Lower-Normandy); O.N (Commissariat à l’Energie Atomique-CEA); M.F. (Centre National de la Recherche scientifique—CNRS); S.L. (Regional council of Lower-Normandy); and C.A. (French Ministry of Education and Research).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Calcium
Excitotoxicity
NMDA
PAI-1
Smad
TGF
t-PA

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10.1006/mcne.2002.1206

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Docagne, F., Nicole, O., Gabriel, C., Fernández-Monreal, M., Lesné, S., Ali, C., Plawinski, L., Carmeliet, P., MacKenzie, E. T., Buisson, A., & Vivien, D. (2002). Smad3-dependent induction of plasminogen activator inhibitor-1 in astrocytes mediates neuroprotective activity of transforming growth factor-β1 against NMDA-induced necrosis. Molecular and Cellular Neuroscience, 21(4), 634-644. https://doi.org/10.1006/mcne.2002.1206

Smad3-dependent induction of plasminogen activator inhibitor-1 in astrocytes mediates neuroprotective activity of transforming growth factor-β1 against NMDA-induced necrosis. / Docagne, Fabian; Nicole, Olivier; Gabriel, Cecilia et al.
In: Molecular and Cellular Neuroscience, Vol. 21, No. 4, 2002, p. 634-644.

Research output: Contribution to journal › Article › peer-review

Docagne, F, Nicole, O, Gabriel, C, Fernández-Monreal, M, Lesné, S, Ali, C, Plawinski, L, Carmeliet, P, MacKenzie, ET, Buisson, A & Vivien, D 2002, 'Smad3-dependent induction of plasminogen activator inhibitor-1 in astrocytes mediates neuroprotective activity of transforming growth factor-β1 against NMDA-induced necrosis', Molecular and Cellular Neuroscience, vol. 21, no. 4, pp. 634-644. https://doi.org/10.1006/mcne.2002.1206

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abstract = "The intravenous injection of the serine protease, tissue-type plasminogen activator (t-PA), has shown to benefit stroke patients by promoting early reperfusion. However, it has recently been suggested that t-PA activity, in the cerebral parenchyma, may also potentiate excitotoxic neuronal death. The present study has dealt with the role of the t-PA inhibitor, PAI-1, in the neuroprotective activity of the cytokine TGF-β1 and focused on the transduction pathway involved in this effect. We demonstrated that PAI-1, produced by astrocytes, mediates the neuroprotective activity of TGF-β1 against N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. This t-PA inhibitor, PAI-1, protected neurons against NMDA-induced neuronal death by modulating the NMDA-evoked calcium influx. Finally, we showed that the activation of the Smad3-dependent transduction pathway mediates the TGF-β-induced up-regulation of PAI-1 and subsequent neuroprotection. Overall, this study underlines the critical role of the t-PA/PAI-1 axis in the regulation of glutamatergic neurotransmission.",

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author = "Fabian Docagne and Olivier Nicole and Cecilia Gabriel and M{\'o}nica Fern{\'a}ndez-Monreal and Sylvain Lesn{\'e} and Carine Ali and Laurent Plawinski and Peter Carmeliet and MacKenzie, \{Eric T.\} and Alain Buisson and Denis Vivien",

note = "Funding Information: The authors were supported by grants from the CNRS and the University of Caen. The following authors received doctoral bursaries: F.D. (Regional council of Lower-Normandy); O.N (Commissariat {\`a} l{\textquoteright}Energie Atomique-CEA); M.F. (Centre National de la Recherche scientifique—CNRS); S.L. (Regional council of Lower-Normandy); and C.A. (French Ministry of Education and Research).",

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AU - Docagne, Fabian

AU - Nicole, Olivier

AU - Gabriel, Cecilia

AU - Fernández-Monreal, Mónica

AU - Lesné, Sylvain

AU - Ali, Carine

AU - Plawinski, Laurent

AU - Carmeliet, Peter

AU - MacKenzie, Eric T.

AU - Buisson, Alain

AU - Vivien, Denis

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PY - 2002

Y1 - 2002

N2 - The intravenous injection of the serine protease, tissue-type plasminogen activator (t-PA), has shown to benefit stroke patients by promoting early reperfusion. However, it has recently been suggested that t-PA activity, in the cerebral parenchyma, may also potentiate excitotoxic neuronal death. The present study has dealt with the role of the t-PA inhibitor, PAI-1, in the neuroprotective activity of the cytokine TGF-β1 and focused on the transduction pathway involved in this effect. We demonstrated that PAI-1, produced by astrocytes, mediates the neuroprotective activity of TGF-β1 against N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. This t-PA inhibitor, PAI-1, protected neurons against NMDA-induced neuronal death by modulating the NMDA-evoked calcium influx. Finally, we showed that the activation of the Smad3-dependent transduction pathway mediates the TGF-β-induced up-regulation of PAI-1 and subsequent neuroprotection. Overall, this study underlines the critical role of the t-PA/PAI-1 axis in the regulation of glutamatergic neurotransmission.

AB - The intravenous injection of the serine protease, tissue-type plasminogen activator (t-PA), has shown to benefit stroke patients by promoting early reperfusion. However, it has recently been suggested that t-PA activity, in the cerebral parenchyma, may also potentiate excitotoxic neuronal death. The present study has dealt with the role of the t-PA inhibitor, PAI-1, in the neuroprotective activity of the cytokine TGF-β1 and focused on the transduction pathway involved in this effect. We demonstrated that PAI-1, produced by astrocytes, mediates the neuroprotective activity of TGF-β1 against N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. This t-PA inhibitor, PAI-1, protected neurons against NMDA-induced neuronal death by modulating the NMDA-evoked calcium influx. Finally, we showed that the activation of the Smad3-dependent transduction pathway mediates the TGF-β-induced up-regulation of PAI-1 and subsequent neuroprotection. Overall, this study underlines the critical role of the t-PA/PAI-1 axis in the regulation of glutamatergic neurotransmission.

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KW - Excitotoxicity

KW - NMDA

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KW - Smad

KW - TGF

KW - t-PA

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JO - Molecular and Cellular Neuroscience

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ER -

Smad3-dependent induction of plasminogen activator inhibitor-1 in astrocytes mediates neuroprotective activity of transforming growth factor-β1 against NMDA-induced necrosis

Abstract

Bibliographical note

UN SDGs

Keywords

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