Shahed University

miR-320 and Inflammation Regulation in Experimental Autoimmune Encephalomyelitis Through Interference With Tumor Growth Factor-? Signaling Pathway

Samira Ghorbani | Mohammad Vojgani | Farideh talebi | ّFarshid Noorbakhsh

Date :  2019/11/27
Publish in :    Immunoregulation
DOI : 10.32598/Immunoregulation.1.4.229
Link : 10.32598/Immunoregulation.1.4.229
Keywords :MicroRNA, Neuroinflammation, Multiple sclerosis, Experimental autoimmune encephalomyelitis, miR- 320

Abstract :
Background: MicroRNAs are small non-coding RNAs that regulate gene expression and involve in many cellular and physiological mechanisms. Recent studies have revealed that dysregulation of microRNAs might contribute to autoimmune disorders such as Multiple Sclerosis (MS). Based on these findings, we examined the potential role of miR-320 isoforms; miR-320-3p and miR-320-5p, in the context of autoimmune neuroinflammation and pathogenesis of EAE, which is an animal model of MS. Materials and Methods: The expression levels of miR-320-3p and miR-320-5p, and their predicted target genes, TGFBR2 and Smad2, were quantified in the CNS tissue in mice with Experimental Autoimmune Encephalomyelitis (EAE) using RT-PCR method. The expression was also examined in splenocytes macrophages and astrocytes. To examine the interaction of miR-320-3p and miR-320-5p with the 3′-UTR of potential target transcripts, the mimic sequences of both isoforms were transfected into splenocytes and then examined by RT-PCR. Results: The expression of both isoforms of miR-320 significantly increased in different phases of EAE and activated lymphocytes, whereas the levels of their predicted target genes, Smad2 and TGFBR2 decreased in these cells. Obtained data revealed that miR-320-5p level significantly increased in activated macrophages and astrocytes; however, the miR 320-3p level did not show significant changes in these cells after Lipopolysaccharide (LPS) stimulation. The levels of TGFBR2 and Smad2 decreased in transfected splenocytes. Conclusion: Our findings suggest that upregulation of miR-320 isoforms might be involved in the neuroinflammation and pathogenesis of MS through targeting and suppression of TGFBR2 and Smad2, i.e. protective genes in MS.

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