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The contribution of epigenetics to the pathogenesis and gender dimorphism of systemic sclerosis: a comprehensive overview.
Therapeutic Advances in Musculoskeletal Disease ( IF 3.4 ) Pub Date : 2020-05-06 , DOI: 10.1177/1759720x20918456
Bianca Saveria Fioretto 1 , Irene Rosa 2 , Eloisa Romano 3 , Yukai Wang 4 , Serena Guiducci 3 , Guohong Zhang 5 , Mirko Manetti 6 , Marco Matucci-Cerinic 3
Affiliation  

Systemic sclerosis (SSc) is a life-threatening connective tissue disorder of unknown etiology characterized by widespread vascular injury and dysfunction, impaired angiogenesis, immune dysregulation and progressive fibrosis of the skin and internal organs. Over the past few years, a new trend of investigations is increasingly reporting aberrant epigenetic modifications in genes related to the pathogenesis of SSc, suggesting that, besides genetics, epigenetics may play a pivotal role in disease development and clinical manifestations. Like many other autoimmune diseases, SSc presents a striking female predominance, and even if the reason for this gender imbalance has yet to be completely understood, it appears that the X chromosome, which contains many gender and immune-related genes, could play a role in such gender-biased prevalence. Besides a short summary of the genetic background of SSc, in this review we provide a comprehensive overview of the most recent insights into the epigenetic modifications which underlie the pathophysiology of SSc. A particular focus is given to genetic variations in genes located on the X chromosome as well as to the main X-linked epigenetic modifications that can influence SSc susceptibility and clinical phenotype. On the basis of the most recent advances, there is realistic hope that integrating epigenetic data with genomic, transcriptomic, proteomic and metabolomic analyses may provide in the future a better picture of their functional implications in SSc, paving the right way for a better understanding of disease pathogenesis and the development of innovative therapeutic approaches.



中文翻译:


表观遗传学对系统性硬化症发病机制和性别二态性的贡献:全面概述。



系统性硬化症(SSc)是一种病因不明的危及生命的结缔组织疾病,其特征是广泛的血管损伤和功能障碍、血管生成受损、免疫失调以及皮肤和内脏器官的进行性纤维化。在过去的几年中,一个新的研究趋势是越来越多地报道与SSc发病机制相关的基因中的异常表观遗传修饰,这表明除了遗传学之外,表观遗传学可能在疾病发展和临床表现中发挥着关键作用。与许多其他自身免疫性疾病一样,SSc 呈现出显着的女性优势,即使这种性别失衡的原因尚未完全了解,但包含许多性别和免疫相关基因的 X 染色体似乎可以发挥作用在这种性别偏见的盛行率中。除了对 SSc 遗传背景的简短总结外,在这篇综述中,我们还全面概述了对 SSc 病理生理学基础的表观遗传修饰的最新见解。特别关注位于 X 染色体上的基因的遗传变异以及可影响 SSc 易感性和临床表型的主要 X 连锁表观遗传修饰。基于最新进展,将表观遗传数据与基因组、转录组、蛋白质组和代谢组分析相结合,有望在未来更好地了解它们在 SSc 中的功能意义,为更好地理解 SSc 铺平正确的道路。疾病发病机制和创新治疗方法的发展。

更新日期:2020-05-06
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