Vitamin D receptor-retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation
Authorde la Fuente, AG; Errea, O; van Wijngaarden, P; Gonzalez, GA; Kerninon, C; Jarjour, AA; Lewis, HJ; Jones, CA; Nait-Oumesmar, B; Zhao, C; ...
Source TitleThe Journal of Cell Biology
PublisherROCKEFELLER UNIV PRESS
University of Melbourne Author/svan Wijngaarden, Peter
AffiliationOphthalmology (Eye & Ear Hospital)
Document TypeJournal Article
Citationsde la Fuente, A. G., Errea, O., van Wijngaarden, P., Gonzalez, G. A., Kerninon, C., Jarjour, A. A., Lewis, H. J., Jones, C. A., Nait-Oumesmar, B., Zhao, C., Huang, J. K., Ffrench-Constant, C. & Franklin, R. 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. https://doi.org/10.1083/jcb.201505119.
Access StatusOpen Access
NHMRC Grant codeNHMRC/628928
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.
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