Schneider Andrew J, Branam Amanda M, Peterson Richard E
School of Pharmacy and Molecular and Environmental Toxicology Center University of Wisconsin, Madison, WI 53705, USA.
Int J Mol Sci. 2014 Oct 3;15(10):17852-85. doi: 10.3390/ijms151017852.
The AHR (aryl hydrocarbon receptor) and Wnt (wingless-related MMTV integration site) signaling pathways have been conserved throughout evolution. Appropriately regulated signaling through each pathway is necessary for normal development and health, while dysregulation can lead to developmental defects and disease. Though both pathways have been vigorously studied, there is relatively little research exploring the possibility of crosstalk between these pathways. In this review, we provide a brief background on (1) the roles of both AHR and Wnt signaling in development and disease, and (2) the molecular mechanisms that characterize activation of each pathway. We also discuss the need for careful and complete experimental evaluation of each pathway and describe existing research that explores the intersection of AHR and Wnt signaling. Lastly, to illustrate in detail the intersection of AHR and Wnt signaling, we summarize our recent findings which show that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced disruption of Wnt signaling impairs fetal prostate development.
芳烃受体(AHR)和Wnt(无翅相关MMTV整合位点)信号通路在整个进化过程中一直保留。通过每条通路进行适当调控的信号传导对于正常发育和健康是必要的,而失调则会导致发育缺陷和疾病。尽管这两条通路都已得到深入研究,但探索这些通路之间相互作用可能性的研究相对较少。在本综述中,我们简要介绍了以下内容:(1)AHR和Wnt信号传导在发育和疾病中的作用,以及(2)表征每条通路激活的分子机制。我们还讨论了对每条通路进行仔细且全面实验评估的必要性,并描述了探索AHR和Wnt信号传导交叉点的现有研究。最后,为详细说明AHR和Wnt信号传导的交叉点,我们总结了我们最近的研究结果,这些结果表明2,3,7,8 - 四氯二苯并 - 对 - 二恶英(TCDD)诱导的Wnt信号传导破坏会损害胎儿前列腺发育。