摘要
甲状腺相关性眼病(TAO)的发生与发展及其表观遗传的关系密切。其中，TAO的发生与脱氧核糖核酸甲基化所引起的差异基因表达、非编码核糖核酸(RNA)调控及微小RNA(miRNA)相关。miRNA－155和miRNA－146a通过参与免疫炎症及脂肪组织的增殖分化等参与TAO的病理过程；miRNA－21的表达与TAO的活动性及严重程度相关；miRNA－130a和miRNA－27在TAO眼眶成纤维细胞的成脂分化及脂肪组织增生中发挥着重要作用；miRNA－199a－3p和miRNA－199a－5p可增加患者眼眶脂肪组织的氧化应激和血管生成；TAO患者的miRNA－183和miRNA－96在外周血分化簇(CD)4+T细胞中表达升高，参与TAO病程的调节免疫；miRNA－29可通过抑制转化生长因子β1信号通路抑制细胞纤维化；miRNA－143可通过直接靶向胰岛素样生长因子－1受体，间接降低促甲状腺素受体和核苷酸结合寡聚域样受体热蛋白结构域相关蛋白3浓度，调节TAO的炎症反应。此外，长链非编码RNA、环状RNA、转运RNA衍生片段及组蛋白修饰的表观遗传调控亦与TAO的发病相关。
Abstract
The occurrence and development of thyroid associated ophthalmopathy (TAO) is related to the differential gene expression caused by DNA methylation, non coding RNA regulation, microRNA (miRNA). The miRNA-155 and miRNA-146a participated in the pathological process by participating in immune inflammation and the proliferation and differentiation of adipose tissue. The expression of miRNA-21 was correlated with the activity and severity of TAO. The miRNA-130a and miRNA-27 play an important role in the adipogenic differentiation of TAO orbital fibroblasts and the proliferation of adipose tissue. The miRNA-199a-3p and 5p increased tissue oxidative stress and angiogenesis in orbital adipocytes of TAO patients. The expression of miRNA-183 and miRNA-96 was increased in peripheral blood CD4+ T cells of TAO patients, which regulate immunity to participate in the progression. The miRNA-29 inhibits cell fibrosis by restricting transforming growth factor-β1 Signal path. The miRNA-143 regulates the inflammatory response by directly targeting insulin like growth factor-1 receptor and indirectly reducing thyrotropin receptor and nucleotide oligomerization domain-like receptor thermal protein domain associated protein 3 levels. In addition, the epigenetic regulation of long chain non coding RNAs, circular RNAs, transfer RNA derived fragments, and histone modification inactivation are also related to the pathogenesis of TAO.
基金项目
山西省中医药管理局科研课题(2020ZYYC059)
山西省医学重点科研项目(2020XM07)
山西省眼科医院科研基金(C202101)
万方数据