Epstein-Barr virus (EBV) is a human herpes virus that latently infects B lymphocytes. When EBV is reactivated, host B cells differentiate into plasma cells and produce IgM-dominant antibodies as well as many progeny virions. The aims of the present study were to confirm the IgM dominance of thyrotropin-receptor antibodies (TRAbs) produced by EBV reactivation and investigate the roles of TRAb-IgM in Graves' disease. Peripheral blood mononuclear cells (PBMCs) containing TRAb-producing cells were stimulated for EBV reactivation, and TRAb-IgM and TRAb-IgG were measured by ELISA. TRAb-IgM were purified and TSH-binding inhibitory activities were assessed using a radio-receptor assay. Porcine thyroid follicular epithelial cells were cultured with TRAb-IgM and/or complements to measure the intracellular levels of cAMP and the amount of LDH released. TRAb-IgM/TRAb-IgG (the MG ratio) was examined in sequential serum samples of Graves' disease and compared among groups of thyroid function. The results obtained showed that IgM-dominant TRAb production was induced by EBV reactivation. TRAb-IgM did not inhibit TSH binding to TSH receptors and did not transduce hormone-producing signals. However, it destroyed thyroid follicular epithelial cells with complements. The MG ratio was significantly higher in samples of hyperthyroidism or hypothyroidism than in those with normal function or in healthy controls. A close relationship was observed between TRAb-IgM produced by EBV reactivation and the development and exacerbation of Graves' disease. The present results provide novel insights for the development of prophylaxis and therapeutics for Graves' disease.
Objective: Skeletal muscle fiber conversion bears a part in multiple myopathies, and one of those is Sarcopenia which is known to correlate with aging, nutritional deficiency, and so on. In this study, we focused on muscle specific enriched microRNAs (myomirs) to understand the mechanisms of muscle fiber conversion.Method & Results: In-silico study, we selected the microRNA-133a-3p (miR-133a), a myomir relevant to the skeletal myogenesis. Using the human iPS cell-derived skeletal myogenesis system, we identified that expression level of miR -133a was elevated with a peak at day 5 after the induction of myogenesis. Overexpression of miR-133a mimic or inhibitor at the beginning of myogenesis increased mRNA expression of Myh7, a specific marker of slow oxidative myotube, or Myh1, a marker of fast-type myotube, respectively. Furthermore, we found that, under the serumdeprived culture condition, overexpression of miR-133a mimic preserved the cell feature of oxidative fibers, although miR-133a inhibition deformed the tubular formation of oxidative myotubes. Conclusion: MicroRNA-133a functioned to buttress the gene expression of oxidative fiber-specified myosin heavy chain, and to preserve myotubes from nutritional stress, suggesting the possibility that miR-133a would be a therapeutic target for sarcopenia.
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