Species generalization and differences in Hedgehog pathway regulation of fungiform and circumvallate papilla taste function and somatosensation demonstrated with sonidegib.
Species generalization and differences in Hedgehog pathway regulation of fungiform and circumvallate papilla taste function and somatosensation demonstrated with sonidegib.
复制标题
DOI：
10.1038/s41598-018-34399-3
复制
发表时间：
2018-11-01
影响因子：
4.6
通讯作者：
Mistretta CM
中科院分区：
文献类型：
--
作者：
Kumari A;Yokota Y;Li L;Bradley RM;Mistretta CM
刺猬通路抑制（HPI）在味觉器官的稳态和感觉中的深刻的、模态特异性的作用中的物种泛化被示出。与HPI，癌症药物sonidegib，我们证明，大鼠味觉系统，除了小鼠，是由刺猬信号调节。在大鼠中，在sonidegib治疗16-36天后，软腭、菌状（FP）和轮廓乳头（CV）中的味蕾（TB）丧失，并且来自鼓索和舌咽神经的味觉反应消除。HPI期间FP和CV中保留的神经支配不能维持TB。对触觉刺激的反应没有改变，温度反应仅在治疗28天后降低，表明了模式特异性效应。大鼠FP和神经效应与小鼠相似，而大鼠CV的TB和神经反应效应严重得多。当在延长的48天HPI后在小鼠中引入恢复时，CV中的TB恢复，而FP中的TB没有。总体而言，刺猬信号调节被证明是推广到大鼠味觉系统，并肯定了味觉器官感觉中的模态特异性控制。基于这些数据，可以更好地理解使用HPI药物的患者中报告的使人衰弱的味觉障碍。
Species generalization in the profound, modality-specific effects of Hedgehog pathway inhibition (HPI) in taste organ homeostasis and sensation is shown. With the HPI, cancer drug sonidegib, we demonstrate that the rat taste system, in addition to mouse, is regulated by Hedgehog signaling. After sonidegib treatment for 16–36 days in rat, there is loss of taste buds (TB) in soft palate, in fungiform (FP) and circumvallate papillae (CV), and elimination of taste responses from chorda tympani and glossopharyngeal nerves. The retained innervation in FP and CV during HPI cannot sustain TB. Responses to tactile stimuli are not altered, and temperature responses are reduced only after 28 days treatment, demonstrating modality-specific effects. Rat FP and neural effects are similar to those in mouse whereas TB and neural response effects from the rat CV are much more severe. When recovery is introduced in mouse after prolonged, 48 days HPI, the TB in CV are restored whereas those in FP are not. Overall, Hedgehog signaling regulation is shown to generalize to the rat taste system, and the modality-specific controls in taste organ sensation are affirmed. The reported, debilitating taste disturbances in patients who use HPI drugs can be better understood based on these data.
登录
查看更多内容
影响因子：
2.4
作者：
Ma H;Yang R;Thomas SM;Kinnamon JC
通讯作者：
Kinnamon JC
影响因子：
16.6
作者：
Dvoryanchikov G;Hernandez D;Roebber JK;Hill DL;Roper SD;Chaudhari N
通讯作者：
Chaudhari N
DOI：
10.1634/theoncologist.2016-0186
发表时间：
2016-10
期刊：
The oncologist
影响因子：
--
作者：
Lacouture ME;Dréno B;Ascierto PA;Dummer R;Basset-Seguin N;Fife K;Ernst S;Licitra L;Neves RI;Peris K;Puig S;Sokolof J;Sekulic A;Hauschild A;Kunstfeld R
通讯作者：
Kunstfeld R
DOI：
10.1111/jdv.14542
发表时间：
2018-03
期刊：
Journal of the European Academy of Dermatology and Venereology : JEADV
影响因子：
--
作者：
Lear JT;Migden MR;Lewis KD;Chang ALS;Guminski A;Gutzmer R;Dirix L;Combemale P;Stratigos A;Plummer R;Castro H;Yi T;Mone M;Zhou J;Trefzer U;Kaatz M;Loquai C;Kudchadkar R;Sellami D;Dummer R
通讯作者：
Dummer R
DOI：
10.1073/pnas.1719109115
发表时间：
2018-01-09
影响因子：
11.1
作者：
Lu, Wan-Jin;Mann, Randall K.;Beachy, Philip A.
通讯作者：
Beachy, Philip A.