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

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.

T lymphocytes and preeclampsia: The potential role of T‐cell subsets and related MicroRNAs in the pathogenesis of preeclampsia

“…According to previous research, miR‐320a has low expression in human non‐small lung cancer cells and acts as a crucial regulator in gastric cancer by targeting Ras‐related protein Rab‐14 117 . Overexpression of miR‐320 isoforms in activated T cells can reduce the TGF‐ β signaling pathway by suppressing TGFBR2 and Smad2 genes 118 . miR‐320a has an important impact on the invasion and proliferation of trophoblast cells 119 .…”

“…117 Overexpression of miR-320 isoforms in activated T cells can reduce the TGFβ signaling pathway by suppressing TGFBR2 and Smad2 genes. 118 miR-320a has an important impact on the invasion and proliferation of trophoblast cells. 119 Recently, it has been found that miR-320a levels increase in serum of PE patients.…”

Circulating miRNAs as Potential Biomarkers Distinguishing Relapsing–Remitting from Secondary Progressive Multiple Sclerosis. A Review

“…Studies on the mice with EAE showed that overexpression of cell-free miR-320 isoforms plays a possible role in the autoimmune neuroinflammation and the pathogenesis of MS disease. Talebi et al found that miR-320 isoforms could target SMAD2 and TGFBR2 (TGF-β Receptor 2), thereby diminishing the TGF-β signaling pathway [ 108 ]. This pathway contributes to the increasing differentiation of naive T cells into Treg cells and inhibition of Th1, leading to the decrease in IFN-γ production and lessening EAE [ 109 ].…”

“…This pathway contributes to the increasing differentiation of naive T cells into Treg cells and inhibition of Th1, leading to the decrease in IFN-γ production and lessening EAE [ 109 ]. As a result, overexpression of miR-320 isoforms might be involved in the neuroinflammation and pathogenesis of MS through reducing neuroprotective and immunomodulatory effects of TGF-β [ 108 ]. Moreover, in B cells of MS patients during a disease relapse, the expression of miR-320a is decreased, leading to increased MMP9 expression, being a marker of disease activity in patients with MS [ 110 , 111 ].…”