75 年糖皮质激素发现之旅:我们对风湿性疾病中糖皮质激素受体机制认识的演变。

IF 20.3 1区 医学 Q1 RHEUMATOLOGY
Ann-Kathrin Eiers, Sabine Vettorazzi, Jan P Tuckermann
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引用次数: 0

摘要

四分之三个世纪以来,糖皮质激素(GCs)一直被用于治疗风湿病和自身免疫性疾病。在这 75 年中,我们对糖皮质激素与核受体(主要是糖皮质激素受体(GR))的结合及其分子机制的认识发生了巨大变化。最初,在 20 世纪 50 年代末,GCs 被认为是能量代谢的重要调节剂。到 20 世纪 70 年代/80 年代,它们被定性为荷尔蒙诱导转录因子的配体,可调节细胞生物学和生理学的许多方面。最近,人们重新发现了它们对细胞代谢的影响。通过使用 Cre/LoxP 系统研究条件性 GR 突变小鼠,我们对关节炎模型中细胞类型特异性 GC 作用以及各种免疫细胞和基质细胞之间的相互影响有了进一步的了解。在研究复杂的细胞类型特异性相互作用方面取得的一项重大成就是最近出现的单细胞分辨率的全息技术,它将为进一步了解介导 GC 反应的细胞类型和因子提供前所未有的洞察力。除了基因编码的因素外,参与解决关节炎期间 GCs 炎症的抗炎代谢物也刚刚被发现。将这些知识转化为治疗概念将有助于解决炎症性疾病并减少副作用。在本综述中,我们将介绍临床前研究的主要里程碑,这些里程碑使我们在首次将 GCs 用于治疗关节炎 75 年后,对 GC 和 GR 的作用有了目前的了解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Journey through discovery of 75 years glucocorticoids: evolution of our knowledge of glucocorticoid receptor mechanisms in rheumatic diseases.

For three-quarters of a century, glucocorticoids (GCs) have been used to treat rheumatic and autoimmune diseases. Over these 75 years, our understanding of GCs binding to nuclear receptors, mainly the glucocorticoid receptor (GR) and their molecular mechanisms has changed dramatically. Initially, in the late 1950s, GCs were considered important regulators of energy metabolism. By the 1970s/1980s, they were characterised as ligands for hormone-inducible transcription factors that regulate many aspects of cell biology and physiology. More recently, their impact on cellular metabolism has been rediscovered. Our understanding of cell-type-specific GC actions and the crosstalk between various immune and stromal cells in arthritis models has evolved by investigating conditional GR mutant mice using the Cre/LoxP system. A major achievement in studying the complex, cell-type-specific interplay is the recent advent of omics technologies at single-cell resolution, which will provide further unprecedented insights into the cell types and factors mediating GC responses. Alongside gene-encoded factors, anti-inflammatory metabolites that participate in resolving inflammation by GCs during arthritis are just being uncovered. The translation of this knowledge into therapeutic concepts will help tackle inflammatory diseases and reduce side effects. In this review, we describe major milestones in preclinical research that led to our current understanding of GC and GR action 75 years after the first use of GCs in arthritis.

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来源期刊
Annals of the Rheumatic Diseases
Annals of the Rheumatic Diseases 医学-风湿病学
CiteScore
35.00
自引率
9.90%
发文量
3728
审稿时长
1.4 months
期刊介绍: Annals of the Rheumatic Diseases (ARD) is an international peer-reviewed journal covering all aspects of rheumatology, which includes the full spectrum of musculoskeletal conditions, arthritic disease, and connective tissue disorders. ARD publishes basic, clinical, and translational scientific research, including the most important recommendations for the management of various conditions.
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