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阻断P2X受体可抑制成年小鼠嗅觉上皮祖细胞损伤诱导的增殖。

Blocking P2X receptors can inhibit the injury-induced proliferation of olfactory epithelium progenitor cells in adult mouse.

作者信息

Gao Liang, Cao Li, Qiu Yang, Su Zhida, Burnstock Geoffrey, Xiang Zhenghua, He Cheng

机构信息

Institute of Neuroscience, Neuroscience Research Center of Changzheng Hospital, Second Military Medical University, Shanghai, China.

出版信息

Int J Pediatr Otorhinolaryngol. 2010 Jul;74(7):747-51. doi: 10.1016/j.ijporl.2010.03.030. Epub 2010 Apr 14.

Abstract

OBJECTIVE

The olfactory epithelium (OE) is unusual for its remarkable regenerative capacity and sustained neurogenesis of olfactory receptor neurons (ORNs) throughout adult life. Regeneration of ORNs is accomplished by basal cells in the OE, including stem cells and progenitor cells. Although there is considerable knowledge about the roles of OE basal cells in ORN turnover, the molecular mechanism that regulates the proliferation and differentiation of adult OE basal cells is not fully understood. As intercellular signaling molecules, purines have been reported to meditate proliferation, differentiation and migration of many kinds of neural stem cells. However, it is still unclear whether ATP, which could be released by injured ORNs, plays a role in regulating neurogenesis in ORN turnover.

METHODS

RT-PCR and immunohistochemistry were used to detect the expression of ionotropic purinergic receptors-P2X receptors in adult mouse OE. By using the olfactory bulbectomy model and in vivo administration of P2X receptors antagonists, the function of P2X receptors in regulating the proliferation of OE progenitor cell was evaluated.

RESULTS

We found that basal cells in the adult mouse OE express functional P2X receptors, and blocking the activities of P2X receptors can significantly inhibit the injury-induced proliferation of OE basal cells.

CONCLUSION

Our research provides evidence in support of the hypothesis that purinergic signaling can serve as a paracrine signal in regulating the neurogenesis of OE in adult mouse.

摘要

目的

嗅上皮(OE)因其显著的再生能力以及成年期嗅受体神经元(ORN)持续的神经发生而与众不同。ORN的再生由OE中的基底细胞完成,包括干细胞和祖细胞。尽管关于OE基底细胞在ORN更替中的作用已有相当多的了解,但调节成年OE基底细胞增殖和分化的分子机制尚未完全清楚。作为细胞间信号分子,嘌呤已被报道可介导多种神经干细胞的增殖、分化和迁移。然而,由受损ORN释放的三磷酸腺苷(ATP)是否在ORN更替过程中调节神经发生仍不清楚。

方法

采用逆转录聚合酶链反应(RT-PCR)和免疫组织化学方法检测成年小鼠OE中离子型嘌呤能受体——P2X受体的表达。通过使用嗅球切除模型和体内给予P2X受体拮抗剂,评估P2X受体在调节OE祖细胞增殖中的功能。

结果

我们发现成年小鼠OE中的基底细胞表达功能性P2X受体,阻断P2X受体的活性可显著抑制损伤诱导的OE基底细胞增殖。

结论

我们的研究为嘌呤能信号传导作为旁分泌信号调节成年小鼠OE神经发生这一假说提供了证据支持。

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