MiR-181a Ameliorates the Progression of Myasthenia Gravis by Regulating TRIM9.

Qiang Wang,Shixiang Kuang,Ruozhao Li,Zhichao Zhou,Yunquan Liu,Ning Weng,Songwen Tan

doi:10.1155/2021/1303375

Abstract

Abnormally activated CD4+ T cells are considered to be an important factor in the pathogenesis of myasthenia gravis (MG). In the pathogenesis of MG, the imbalance of proinflammatory cytokines and immune cells maintains the imbalance of immune response and inflammatory microenvironment. Studies have shown that miRNA is involved in the pathogenesis of MG. In our experiment, we extracted peripheral blood mononuclear cells (PBMCs) from MG patients and detected the expression of miR-181a and TRIM9 in PBMCs by qRT-PCR. In vitro experiments were conducted to explore the regulatory mechanism of miR-181a on target genes and its influence on inflammatory factors related to MG disease. Experimental autoimmune myasthenia gravis (EAMG) model mice are established, and the effects of miR-181a on EAMG symptoms and inflammatory factors are explored through in vivo experiments. According to a total of 40 EAMG mice that were successfully modeled, all EAMG mice showed symptoms of muscle weakness; their diet was reduced; their weight gain was slow; and even weight loss occurred. In MG patients and EAMG mice, the expression of miR-181a was low and TRIM9 was highly expressed. Bioinformatics website and dual-luciferase report analysis of miR-181a had a targeting relationship with TRIM9, and miR-181a could target the expression of TRIM9. After upregulating miR-181a or interfering with TRIM9, serum miR-181a in EAMG mice was significantly upregulated; TRIM9 was significantly downregulated; its clinical symptoms were reduced; and the expression of inflammatory factors was reduced. The study finally learned that miR-181a can reduce the level of MG inflammatory factors by targeting the expression of TRIM9 and has the effect of improving the symptoms of MG.

Highlights

Myasthenia gravis (MG) is an acquired autoimmune disease. e postsynaptic membrane of the neuromuscular junction (NMJ) is the site of its disease
Detecting the expression of miR-181a and TRIM9 in MG patients, it was found that miR-181a was low in MG and TRIM9 was high in MG, both of which were statistically significant (P < 0.05; Figures 1(a) and 1(b))
Establishment of the Experimental autoimmune myasthenia gravis (EAMG) Model. ere were a total of 45 mice in the model group who have the disease, and the success rate of modeling was about 72.58%

Summary

Introduction

Myasthenia gravis (MG) is an acquired autoimmune disease. e postsynaptic membrane of the neuromuscular junction (NMJ) is the site of its disease. Myasthenia gravis (MG) is an acquired autoimmune disease. E postsynaptic membrane of the neuromuscular junction (NMJ) is the site of its disease. When the acetylcholine receptor (AchR) on the postsynaptic membrane is destroyed, the number of this receptor decreases, leading to the occurrence of myasthenia gravis [1]. Skeletal muscle is the main organ involved in myasthenia gravis, and other organs can be affected by it. E most serious consequence of the disease is muscle weakness crisis. Is disease can occur in any age group, but a large number of clinical studies have found that 20–40 years old and 40–60 years old are the two peak incidences of myasthenia gravis. MG patients between the ages 20 and 40 are more common in women, and the onset of men is between 40 and 60 years.

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Conclusion