Faculty of Health and Life Sciences, Northumbria University, Ellison Building, Tyne and Wear, Newcastle upon Tyne NE2 8ST, UK.
Department of Internal Medicine 3, Erlangen University, Erlangen, Germany.
Trends Mol Med. 2019 May;25(5):395-411. doi: 10.1016/j.molmed.2019.02.001. Epub 2019 Mar 8.
Systemic sclerosis (SSc) is a rare autoimmune disorder characterised by skin fibrosis that often also affects internal organs, eventually resulting in mortality. Although management of the symptoms has extended lifespan, patients still suffer from poor quality of life, hence the need for improved therapies. Development of efficacious treatments has been stymied by the unknown aetiology, although recent advancements suggest a potentially key role for epigenetics - the regulation of gene expression by noncoding RNAs and chemical modifications to DNA or DNA-associated proteins. Herein, the evidence implicating epigenetics in the pathogenesis of SSc is discussed with an emphasis on the therapeutic potential this introduces to the field - particularly the repurposing of epigenetic targeting cancer therapeutics and newly emerging miRNA-based strategies.
系统性硬化症（SSc）是一种罕见的自身免疫性疾病，其特征是皮肤纤维化，通常也会影响内脏器官，最终导致死亡。尽管对症状的治疗已经延长了患者的寿命，但他们的生活质量仍然很差，因此需要改进治疗方法。尽管最近的进展表明，非编码 RNA 以及 DNA 或 DNA 相关蛋白的化学修饰对基因表达的调控可能具有潜在的关键作用，但由于病因不明，有效的治疗方法的开发一直受到阻碍。本文讨论了表观遗传学在 SSc 发病机制中的作用，并强调了这一作用在该领域带来的治疗潜力——特别是重新利用表观遗传靶向癌症治疗药物和新出现的基于 microRNA 的策略。
