期刊
JOURNAL OF CELL BIOLOGY
卷 211, 期 5, 页码 975-985出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201505119
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资金
- United Kingdom Multiple Sclerosis Society
- Wellcome Trust
- Sir David and Isobel Walker Trust
- Medical Research Council
- Investissements d'avenir Instituts Hospitalo-Universitaires A Institut du Cerveau et de la Moelle Epiniere
- National Health and Medical Research Council [628928]
- Obra Social La Caixa
- MRC [MC_PC_12012] Funding Source: UKRI
- Medical Research Council [MC_PC_12012] Funding Source: researchfish
- Rosetrees Trust [M144] Funding Source: researchfish
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 gamma (RXR-gamma) has been shown to be a positive regulator of OPC differentiation. However, the nuclear receptor (NR) binding partner of RXR-gamma has not been established. In this study we show that RXR-gamma 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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