Osteopontin is induced by TGF-?2 and regulates metabolic cell activity in cultured human optic nerve head astrocytes

Neumann C, Garreis F, Paulsen F, Hammer C, Birke MT, Scholz M (2014)

Publication Type: Journal article

Publication year: 2014

Journal

PLoS ONE Public Library of Science

Book Volume: 9

Pages Range: e92762

Journal Issue: 4

DOI: 10.1371/journal.pone.0092762

Abstract

The aqueous humor (AH) component transforming growth factor (TGF)-?2 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-?2 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 ?V, ?4, ? 5, ?6, ?9, ?1, ?3 and ?5 by ONH astrocytes were shown by sqRT-PCR and immunofluorescence labeling. TGF-?2 treatment did not affect their expression levels. OPN did not regulate gene expression of described TGF-?2 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-?2 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-?2 responsive factor that is not involved in TGF-?2 mediated ECM and HSP modulation, but affects the metabolic activity of astrocytes. A potential involvement in a protective response to TGF-?2 triggered damage is indicated, but requires further investigation.

Authors with CRIS profile

Fabian Garreis Lehrstuhl für Funktionelle und Klinische Anatomie Friedrich Paulsen Lehrstuhl für Funktionelle und Klinische Anatomie Christian Hammer Lehrstuhl für Funktionelle und Klinische Anatomie Michael Scholz Lehrstuhl für Funktionelle und Klinische Anatomie

Involved external institutions

Tufts University US United States (USA) (US)

How to cite

APA:

Neumann, C., Garreis, F., Paulsen, F., Hammer, C., Birke, M.T., & Scholz, M. (2014). Osteopontin is induced by TGF-?2 and regulates metabolic cell activity in cultured human optic nerve head astrocytes. PLoS ONE, 9(4), e92762. https://doi.org/10.1371/journal.pone.0092762

MLA:

Neumann, Carolin, et al. "Osteopontin is induced by TGF-?2 and regulates metabolic cell activity in cultured human optic nerve head astrocytes." PLoS ONE 9.4 (2014): e92762.

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