AP1 transcription factors are required to maintain the peripheral taste system.

AP1 transcription factors are required to maintain the peripheral taste system.
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DOI:
10.1038/cddis.2016.343
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发表时间:
2016-10-27
影响因子:
9
通讯作者:
--
中科院分区:
生物学1区
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--
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味觉被生物体用来达到最佳的营养需求,并避免潜在的有毒化合物。在口腔中,味觉感受器细胞聚集在一起形成味蕾,味蕾存在于舌头中的特化味觉乳头中。味觉感受器细胞是检测潜在食物中的化学物质并将该信息传递给味觉神经的细胞,味觉神经将味觉信息传递给大脑。由于味觉细胞与外部环境接触,它们可能会受损,并在生物体的整个生命周期中定期更换以维持功能。然而,这种味觉细胞更新随着时间的推移而失去效率,导致味觉能力的降低。目前,人们对调节味觉细胞更新和维持的机制知之甚少。因此,我们对2个月和6个月大的小鼠分离的味觉细胞进行了RNA测序分析,以确定味觉细胞转录组的改变如何调节成年人的味觉细胞维持和功能。我们发现,激活蛋白-1(AP 1)转录因子(c-Fos,Fosb和c-Jun)和与此途径相关的基因在6个月时在味觉细胞中显著下调,并在12个月时进一步下降。我们产生了条件性c-Fos敲除小鼠,以靶向K14表达细胞,包括分化的味觉细胞。c-Fos基因的缺失导致了味蕾结构的严重紊乱,并导致了味蕾大小的显著减小。c-Fos缺失也影响了味觉细胞的周转,如增殖标记物的减少和凋亡标记物裂解的PARP的上调所证明的。因此,AP 1因子是成人味觉细胞更新的重要调节因子,其下调对味觉维持产生负面影响。
The sense of taste is used by organisms to achieve the optimal nutritional requirement and avoid potentially toxic compounds. In the oral cavity, taste receptor cells are grouped together in taste buds that are present in specialized taste papillae in the tongue. Taste receptor cells are the cells that detect chemicals in potential food items and transmit that information to gustatory nerves that convey the taste information to the brain. As taste cells are in contact with the external environment, they can be damaged and are routinely replaced throughout an organism's lifetime to maintain functionality. However, this taste cell turnover loses efficiency over time resulting in a reduction in taste ability. Currently, very little is known about the mechanisms that regulate the renewal and maintenance of taste cells. We therefore performed RNA-sequencing analysis on isolated taste cells from 2 and 6-month-old mice to determine how alterations in the taste cell-transcriptome regulate taste cell maintenance and function in adults. We found that the activator protein-1 (AP1) transcription factors (c-Fos, Fosb and c-Jun) and genes associated with this pathway were significantly downregulated in taste cells by 6 months and further declined at 12 months. We generated conditional c-Fos-knockout mice to target K14-expressing cells, including differentiating taste cells. c-Fos deletion caused a severe perturbation in taste bud structure and resulted in a significant reduction in the taste bud size. c-Fos deletion also affected taste cell turnover as evident by a decrease in proliferative marker, and upregulation of the apoptotic marker cleaved-PARP. Thus, AP1 factors are important regulators of adult taste cell renewal and their downregulation negatively impacts taste maintenance.
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