New Trends in Aryl Hydrocarbon Receptor Biology.
New Trends in Aryl Hydrocarbon Receptor Biology.
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DOI：
10.3389/fcell.2016.00045
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发表时间：
2016
影响因子：
5.5
通讯作者：
Fernandez-Salguero PM
中科院分区：
文献类型：
--
作者：
Mulero-Navarro S;Fernandez-Salguero PM
传统上被认为是二恶英（2，3，7，8-四氯二苯并对二恶英，TCDD）毒性和致癌反应的关键中间体，芳烃/二恶英受体（AhR）已被证明也是细胞生理和器官稳态的重要调节剂。AhR已成为一个有趣和实际的研究领域，主要是由大量最近的研究分析其对免疫，肝脏，心血管，血管和生殖系统正常功能的贡献推动的。在细胞水平，AhR与控制细胞增殖和细胞周期、细胞形态、细胞粘附和细胞迁移的信号通路建立功能性相互作用。AhR生物学中两个令人兴奋的新方面涉及其在细胞分化控制中的意义以及其更可能参与细胞多能性和干细胞性。事实上，AhR可能有助于调节正常和转化肿瘤细胞中分化和多能性之间的平衡。在分子水平上，AhR通过传统的转录依赖性机制或通过涉及基因组绝缘体、染色质动力学和移动的遗传元件的转录的不可预见的过程来调节越来越大的生理相关基因阵列。AhR也与表观遗传学密切相关，不仅从靶基因表达的角度来看，而且还涉及其自身通过启动子甲基化的调节。有理由认为，这些功能的失调可能具有致病作用，或至少有助于人类疾病。因此，一些实验室已经提出AhR可以作为人类病理学中的诊断标记物和/或治疗靶标的有价值的工具。另一个感兴趣的点是通过饮食中可能存在或包含的内源性无毒低分子量激动剂或拮抗剂分子调节AhR活性的可能性。在这篇综述中，我们将讨论这些分子和功能的AhR生物学的生理和病理背景下的功能。
Traditionally considered as a critical intermediate in the toxic and carcinogenic response to dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD), the Aryl hydrocarbon/Dioxin receptor (AhR) has proven to be also an important regulator of cell physiology and organ homeostasis. AhR has become an interesting and actual area of research mainly boosted by a significant number of recent studies analyzing its contribution to the proper functioning of the immune, hepatic, cardiovascular, vascular and reproductive systems. At the cellular level, AhR establishes functional interactions with signaling pathways governing cell proliferation and cell cycle, cell morphology, cell adhesion and cell migration. Two exciting new aspects in AhR biology deal with its implication in the control of cell differentiation and its more than likely involvement in cell pluripotency and stemness. In fact, it is possible that AhR could help modulate the balance between differentiation and pluripotency in normal and transformed tumor cells. At the molecular level, AhR regulates an increasingly large array of physiologically relevant genes either by traditional transcription-dependent mechanisms or by unforeseen processes involving genomic insulators, chromatin dynamics and the transcription of mobile genetic elements. AhR is also closely related to epigenetics, not only from the point of view of target gene expression but also with respect to its own regulation by promoter methylation. It is reasonable to consider that deregulation of these many functions could have a causative role, or at least contribute to, human disease. Consequently, several laboratories have proposed that AhR could be a valuable tool as diagnostic marker and/or therapeutic target in human pathologies. An additional point of interest is the possibility of regulating AhR activity by endogenous non-toxic low weight molecules agonist or antagonist molecules that could be present or included in the diet. In this review, we will address these molecular and functional features of AhR biology within physiological and pathological contexts.