Vitamin D receptor-retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation

De La Fuente, Alerie Guzman, Errea, Oihana, Van Wijngaarden, Peter, Gonzalez, Ginez A., Kerninon, Christophe, Jarjour, Andrew A., Lewis, Hilary J., Jones, Clare A., Nait-Oumesmar, Brahim, Zhao, Chao, Huang, Jeffrey K., Ffrench-Constant, Charles ORCID: https://orcid.org/0000-0002-5621-3377 and Franklin, Robin J.M. (2015) Vitamin D receptor-retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation. Journal of Cell Biology, 211 (5). pp. 975-985. ISSN 0021-9525

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Abstract

The mechanisms regulating differentiation of oligodendrocyte (OLG) progenitor cells (OPCs) into mature OLGs are key to understanding myelination and remyelination. Signaling via the retinoid X receptor γ (RXR-γ) has been shown to be a positive regulator of OPC differentiation. However, the nuclear receptor (NR) binding partner of RXR-γ has not been established. In this study we show that RXR-γ binds to several NRs in OPCs and OLGs, one of which is vitamin D receptor (VDR). Using pharmacological and knockdown approaches we show that RXR-VDR signaling induces OPC differentiation and that VDR agonist vitamin D enhances OPC differentiation. We also show expression of VDR in OLG lineage cells in multiple sclerosis. Our data reveal a role for vitamin D in the regenerative component of demyelinating disease and identify a new target for remyelination medicines.

Item Type: Article
Uncontrolled Keywords: cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1307
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 15 Jul 2022 22:30
Last Modified: 12 Aug 2022 05:38
URI: https://ueaeprints.uea.ac.uk/id/eprint/86254
DOI: 10.1083/jcb.201505119

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