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.

Transcriptome Profiling of Atlantic Salmon (Salmo salar) Parr With Higher and Lower Pathogen Loads Following Piscirickettsia salmonis Infection

“…Saa5 plays a significant role in the acute phase response in animals suffering from infection or injury, and its transcript levels increased dramatically in rainbow trout with Yersinia ruckeri infection (66). In mammals, GSN is a crucial regulator of actin filament assembly and disassembly; however, recent evidence from mammals suggests that GSN inhibits the inflammatory and cytokine response induced by LPS and overexpression of GSN decreases inflammation and apoptosis in experimental allergic encephalomyelitis animals (67,68). Moreover, in agreement with our results, Eslamloo et al (31) also showed the decreased expression of gsn in Atlantic salmon infected with R. salmoninarum.…”

Structure, regulation and related diseases of the actin-binding protein gelsolin

“…Furthermore, the combination of vitamin D and overexpressing GSN-lentiviruses causes a reduction of inflammation and even a delay in the onset of EAE in tested rats (Ref. 103).…”

Proteomics‐based screening of the target proteins associated with antidepressant‐like effect and mechanism of Saikosaponin A

“…Western blot was performed to verify the protein expression level of PRRT2 in hippocampus. The Western blotting analysis was carried out as previously described with minor modifications. Briefly, the rat hippocampus tissues were homogenized in 500 μL ice‐cold RIPA lysis buffer (Beyotime, Shenzhen, Guangdong, China) using a tissue homogenizer, followed by sonication for 10 s and centrifugation (20 min, 15 000 rpm, 4°C).…”