Targeting NR4A Nuclear Receptors to Control Stromal Cell Inflammation, Metabolism, Angiogenesis, and Tumorigenesis.
Targeting NR4A Nuclear Receptors to Control Stromal Cell Inflammation, Metabolism, Angiogenesis, and Tumorigenesis.
复制标题
DOI：
10.3389/fcell.2021.589770
复制
发表时间：
2021
影响因子：
5.5
通讯作者：
Murphy EP
中科院分区：
文献类型：
--
作者：
Crean D;Murphy EP
NR4A1–NR4A3（Nur77、Nurr1 和 Nor-1）核受体亚家族是一组由多效性刺激（包括肽激素、生长因子、细胞因子、炎症和生理刺激以及细胞应激）诱导的早期基因。 NR4A 受体作为细胞微环境变化的有效传感器，通过基因组和非基因组作用来控制生理和病理过程。 NR4A 受体控制新陈代谢以及心血管和神经功能，并介导炎症和癌症中的免疫细胞稳态。该受体亚家族越来越被认为是慢性炎症、免疫细胞反应改变和癌症发展之间的重要分子联系。在这篇综述中，我们研究了转录组分析如何识别 NR4A1/NR4A2 受体作为间充质基质细胞 (MSC) 迁移、细胞周期进程和细胞因子产生中的转录调节因子，以控制局部免疫反应。在类风湿关节炎等慢性炎症条件下，NR4A 受体已被证明可以改变 MSC 和成纤维细胞样基质细胞的活性，从而调节体内滑膜组织增生、病理性血管生成和软骨更新。此外，由于 NR4A1 已被观察为控制肿瘤发生的肿瘤-基质通讯中的主要转录调节因子，我们讨论了这些受体的药理学控制的进展如何为理解肿瘤微环境在健康和疾病中的作用带来重要的新机制见解。
The NR4A1–NR4A3 (Nur77, Nurr1, and Nor-1) subfamily of nuclear receptors is a group of immediate early genes induced by a pleiotropy of stimuli including peptide hormones, growth factors, cytokines, inflammatory, and physiological stimuli, and cellular stress. NR4A receptors function as potent sensors of changes in the cellular microenvironment to control physiological and pathological processes through genomic and non-genomic actions. NR4A receptors control metabolism and cardiovascular and neurological functions and mediate immune cell homeostasis in inflammation and cancer. This receptor subfamily is increasingly recognized as an important molecular connection between chronic inflammation, altered immune cell responses, and cancer development. In this review, we examine how transcriptome analysis identified NR4A1/NR4A2 receptors as transcriptional regulators in mesenchymal stromal cell (MSC) migration, cell cycle progression, and cytokine production to control local immune responses. In chronic inflammatory conditions, such as rheumatoid arthritis, NR4A receptors have been shown to modify the activity of MSC and fibroblast-like stromal cells to regulate synovial tissue hyperplasia, pathological angiogenesis, and cartilage turnover in vivo. Additionally, as NR4A1 has been observed as a major transcriptional regulator in tumor–stromal communication controlling tumorigenesis, we discuss how advances in the pharmacological control of these receptors lead to important new mechanistic insights into understanding the role of the tumor microenvironment in health and disease.
登录
查看更多内容
DOI：
10.1016/j.jsbmb.2009.12.001
发表时间：
2010-02-28
影响因子：
4.1
作者：
Ghosh, Sagar;Hu, Yanfen;Li, Rong
通讯作者：
Li, Rong
DOI：
10.1158/1541-7786.mcr-16-0436
发表时间：
2017-04
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
de Groot AE;Roy S;Brown JS;Pienta KJ;Amend SR
通讯作者：
Amend SR
影响因子：
4.6
作者：
Hedrick E;Lee SO;Safe S
通讯作者：
Safe S
影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF
影响因子：
5.3
作者：
Hedrick, Erik;Safe, Stephen
通讯作者：
Safe, Stephen