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Vitamin D-binding Protein in Cerebrospinal Fluid is Associated with Multiple Sclerosis Progression

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Abstract

Multiple sclerosis is a neurological disorder that presents with symptoms including inflammation, neurodegeneration, and demyelination of the central nervous system (CNS). Secondary progressive multiple sclerosis (SPMS) manifests with serious physical disability. To quantitatively analyze differential protein expression in patients with SPMS, we performed two-dimensional fluorescence difference in-gel electrophoresis, followed by mass spectrometry on the cerebrospinal fluid of these patients and patients with other neurological diseases. Vitamin D-binding protein (DBP), gelsolin, albumin, etc. showed more than a 1.5-fold difference between the two groups. Based on these results, an experimental allergic encephalomyelitis (EAE) model of multiple sclerosis in Lewis rats was used to investigate DBP’s role in the disease. Protein levels, mRNA transcripts, and ligands of DBP in different regions of the CNS were evaluated under various vitamin D intake levels. Here, DBP levels increased in the experimental rat groups compared to the control groups regardless of vitamin D intake. Moreover, DBP mRNA levels varied in different parts of the CNS including spinal cords in the experimental groups. The observed differences between DBP protein and mRNA levels in the experimental groups’ spinal cords could be derived from the disruption of the blood–brain barrier. Furthermore, an interaction between DBP and actin was confirmed using coimmunoprecipitation and western blot. These results indicate a role for DBP in the actin scavenge system. Moreover, in the experimental group that received oral vitamin D3 supplement, we observed both delayed onset and diminished severity of the disease. When DBP was upregulated, however, the benefits from the vitamin D3 supplements were lost. Thus, we inferred that high levels of DBP were adverse to recovery. In conclusion, here we observed upregulated DBP in the cerebrospinal fluid could serve as a specific diagnostic biomarker for the progression of multiple sclerosis. Next, we demonstrate the vital function of increased levels of free vitamin D metabolites for multiple sclerosis treatment. Finally, vitamin D supplements may be particularly beneficial for SPMS patients.

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Abbreviations

SPMS:

Secondary progressive multiple sclerosis

EAE:

Experimental allergic encephalomyelitis

2-D DIGE:

Two-dimensional fluorescence difference in-gel electrophoresis

DBP:

Vitamin D-binding protein

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Acknowledgments

We wish to thank the department of neurology of Shandong Provincial Hospital for supplying CSF samples. We also acknowledge the Laboratory of Systems Biology, Institute of Biomedical Sciences of Fudan University for providing MALDI-TOF/MS instruments.

Funding

This work was supported by the grants from Natural Science Foundation of China (to Shi-lian LIU; nos. 81070952 and 81271319).

Author information

Authors and Affiliations

  1. Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong, 250012, People’s Republic of China

    Mingchong Yang, YanYan Zhu & Shilian Liu

  2. Laboratory of Systems Biology, Institute of Biomedical Sciences, Fudan University, Shanghai, 200032, China

    Zhaoyu Qin

  3. Department of Clinical Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250011, China

    Yun Li

  4. Department of Neurology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China

    Yanjiang Qin

  5. Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, 250013, China

    Yongsheng Jing

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  1. Mingchong Yang
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  2. Zhaoyu Qin
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  4. Yun Li
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Corresponding author

Correspondence to Shilian Liu.

Additional information

Mingchong Yang and Zhaoyu Qin contributed equally to this work.

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Yang, M., Qin, Z., Zhu, Y. et al. Vitamin D-binding Protein in Cerebrospinal Fluid is Associated with Multiple Sclerosis Progression. Mol Neurobiol 47, 946–956 (2013). https://doi.org/10.1007/s12035-012-8387-1

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