title: Vitamin D-binding protein in cerebrospinal fluid is associated with multiple sclerosis progression.
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.
authors: Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong 250012, People's Republic of China.
authors: Mingchong
authors: M
authors: Yang
authors: Zhaoyu
authors: Z
authors: Qin
authors: Yanyan
authors: Y
authors: Zhu
authors: Yun
authors: Y
authors: Li
authors: Yanjiang
authors: Y
authors: Qin
authors: Yongsheng
authors: Y
authors: Jing
authors: Shilian
authors: S
authors: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015153:Blotting, Western; D002762:Cholecalciferol / Q000494:pharmacology; D004195:Disease Models, Animal; D018450:Disease Progression; D015180:Electrophoresis, Gel, Two-Dimensional; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000134:cerebrospinal fluid / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects; D014809:Vitamin D-Binding Protein / Q000134:cerebrospinal fluid* / Q000737:chemistry
chemical_list: D015415:Biomarkers; D014809:Vitamin D-Binding Protein; D002762:Cholecalciferol