Osteopontin is induced by TGF-β2 and regulates metabolic cell activity in cultured human optic nerve head astrocytes.

The aqueous humor (AH) component transforming growth factor (TGF)-β2 is strongly correlated to primary open-angle glaucoma (POAG), and was shown to up-regulate glaucoma-associated extracellular matrix (ECM) components, members of the ECM degradation system and heat shock proteins (HSP) in primary oc...

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Main Authors: Carolin Neumann, Fabian Garreis, Friedrich Paulsen, Christian M Hammer, Marco T Birke, Michael Scholz
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092762&type=printable
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author Carolin Neumann
Fabian Garreis
Friedrich Paulsen
Christian M Hammer
Marco T Birke
Michael Scholz
author_facet Carolin Neumann
Fabian Garreis
Friedrich Paulsen
Christian M Hammer
Marco T Birke
Michael Scholz
author_sort Carolin Neumann
collection DOAJ
description The aqueous humor (AH) component transforming growth factor (TGF)-β2 is strongly correlated to primary open-angle glaucoma (POAG), and was shown to up-regulate glaucoma-associated extracellular matrix (ECM) components, members of the ECM degradation system and heat shock proteins (HSP) in primary ocular cells. Here we present osteopontin (OPN) as a new TGF-β2 responsive factor in cultured human optic nerve head (ONH) astrocytes. Activation was initially demonstrated by Oligo GEArray microarray and confirmed by semiquantitative (sq) RT-PCR, realtime RT-PCR and western blot. Expressions of most prevalent OPN receptors CD44 and integrin receptor subunits αV, α4, α 5, α6, α9, β1, β3 and β5 by ONH astrocytes were shown by sqRT-PCR and immunofluorescence labeling. TGF-β2 treatment did not affect their expression levels. OPN did not regulate gene expression of described TGF-β2 targets shown by sqRT-PCR. In MTS-assays, OPN had a time- and dose-dependent stimulating effect on the metabolic activity of ONH astrocytes, whereas TGF-β2 significantly reduced metabolism. OPN signaling via CD44 mediated a repressive outcome on metabolic activity, whereas signaling via integrin receptors resulted in a pro-metabolic effect. In summary, our findings characterize OPN as a TGF-β2 responsive factor that is not involved in TGF-β2 mediated ECM and HSP modulation, but affects the metabolic activity of astrocytes. A potential involvement in a protective response to TGF-β2 triggered damage is indicated, but requires further investigation.
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spelling doaj-art-d7492ef43aee41f186e0cc4995ac540b2025-08-20T03:00:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9276210.1371/journal.pone.0092762Osteopontin is induced by TGF-β2 and regulates metabolic cell activity in cultured human optic nerve head astrocytes.Carolin NeumannFabian GarreisFriedrich PaulsenChristian M HammerMarco T BirkeMichael ScholzThe aqueous humor (AH) component transforming growth factor (TGF)-β2 is strongly correlated to primary open-angle glaucoma (POAG), and was shown to up-regulate glaucoma-associated extracellular matrix (ECM) components, members of the ECM degradation system and heat shock proteins (HSP) in primary ocular cells. Here we present osteopontin (OPN) as a new TGF-β2 responsive factor in cultured human optic nerve head (ONH) astrocytes. Activation was initially demonstrated by Oligo GEArray microarray and confirmed by semiquantitative (sq) RT-PCR, realtime RT-PCR and western blot. Expressions of most prevalent OPN receptors CD44 and integrin receptor subunits αV, α4, α 5, α6, α9, β1, β3 and β5 by ONH astrocytes were shown by sqRT-PCR and immunofluorescence labeling. TGF-β2 treatment did not affect their expression levels. OPN did not regulate gene expression of described TGF-β2 targets shown by sqRT-PCR. In MTS-assays, OPN had a time- and dose-dependent stimulating effect on the metabolic activity of ONH astrocytes, whereas TGF-β2 significantly reduced metabolism. OPN signaling via CD44 mediated a repressive outcome on metabolic activity, whereas signaling via integrin receptors resulted in a pro-metabolic effect. In summary, our findings characterize OPN as a TGF-β2 responsive factor that is not involved in TGF-β2 mediated ECM and HSP modulation, but affects the metabolic activity of astrocytes. A potential involvement in a protective response to TGF-β2 triggered damage is indicated, but requires further investigation.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092762&type=printable
spellingShingle Carolin Neumann
Fabian Garreis
Friedrich Paulsen
Christian M Hammer
Marco T Birke
Michael Scholz
Osteopontin is induced by TGF-β2 and regulates metabolic cell activity in cultured human optic nerve head astrocytes.
PLoS ONE
title Osteopontin is induced by TGF-β2 and regulates metabolic cell activity in cultured human optic nerve head astrocytes.
title_full Osteopontin is induced by TGF-β2 and regulates metabolic cell activity in cultured human optic nerve head astrocytes.
title_fullStr Osteopontin is induced by TGF-β2 and regulates metabolic cell activity in cultured human optic nerve head astrocytes.
title_full_unstemmed Osteopontin is induced by TGF-β2 and regulates metabolic cell activity in cultured human optic nerve head astrocytes.
title_short Osteopontin is induced by TGF-β2 and regulates metabolic cell activity in cultured human optic nerve head astrocytes.
title_sort osteopontin is induced by tgf β2 and regulates metabolic cell activity in cultured human optic nerve head astrocytes
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092762&type=printable
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AT friedrichpaulsen osteopontinisinducedbytgfb2andregulatesmetaboliccellactivityinculturedhumanopticnerveheadastrocytes
AT christianmhammer osteopontinisinducedbytgfb2andregulatesmetaboliccellactivityinculturedhumanopticnerveheadastrocytes
AT marcotbirke osteopontinisinducedbytgfb2andregulatesmetaboliccellactivityinculturedhumanopticnerveheadastrocytes
AT michaelscholz osteopontinisinducedbytgfb2andregulatesmetaboliccellactivityinculturedhumanopticnerveheadastrocytes