title: Overexpression of GSN could decrease inflammation and apoptosis in EAE and may enhance vitamin D therapy on EAE/MS.
abstract: The decrease of gelsolin (GSN) in the blood has been reported in multiple sclerosis (MS) patients and experimental allergic encephalomyelitis (EAE) animals, but the protective effect of GSN on EAE/MS lacks of evidence. In our study, we increased the GSN level in EAE by injecting GSN-overexpress lentivirus (LV-GSN) into the lateral ventricle and caudal vein and found that GSN administration can delay the onset and decrease the severity of EAE. Vitamin D is proven to have a therapeutic effect on MS/EAE; however, we previously found that vitamin D caused a downregulation of GSN, which might limit vitamin D efficacy. In our current research, we obtained a better symptom and a slowing down progression in EAE after combining vitamin D treatment with a proper increase of GSN. Furthermore, we discovered that the mediation of vitamin D on GSN might occur through the vitamin D receptor (VDR) by using gene interruption and overexpression to regulate the level of VDR in PC12 cells (a rat sympathetic nerve cell line). We also confirmed the anti-apoptotic function of GSN by GSN RNA interference in PC12. Collectively, these results support the therapeutic effect of GSN in EAE, which might enhance Vitamin D therapy in EAE/MS.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, 44#Wenhua Xi Road, Jinan, 250012, Shandong, P.R. China.
authors.forename: Jifang
authors.initials: J
authors.lastname: Gao
authors.affiliation: Laboratory of Systems Biology, Institute of Biomedical Sciences, Fudan University, 138# Medical School Road, Shanghai, 200032, China.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, 44#Wenhua Xi Road, Jinan, 250012, Shandong, P.R. China.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Guan
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, 44#Wenhua Xi Road, Jinan, 250012, Shandong, P.R. China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Guo
authors.affiliation: Shouguang Century School, 789#Nongsheng Street, Shouguang, 262700, Shandong, China.
authors.forename: Huaqing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, 44#Wenhua Xi Road, Jinan, 250012, Shandong, P.R. China. liushilian@sdu.edu.cn.
authors.forename: Shilian
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018260:Gelsolin / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D051381:Rats; D018167:Receptors, Calcitriol / Q000378:metabolism; D012720:Severity of Illness Index; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014807:Vitamin D / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D018260:Gelsolin; D018167:Receptors, Calcitriol; D014409:Tumor Necrosis Factor-alpha; D014807:Vitamin D