An IP3R3- and NPY-expressing microvillous cell mediates tissue homeostasis and regeneration in the mouse olfactory epithelium.
An IP3R3- and NPY-expressing microvillous cell mediates tissue homeostasis and regeneration in the mouse olfactory epithelium.
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DOI：
10.1371/journal.pone.0058668
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hegg CC
中科院分区：
文献类型：
--
作者：
Jia C;Hayoz S;Hutch CR;Iqbal TR;Pooley AE;Hegg CC
神经营养因子的钙依赖性释放在神经元的维持中起着重要作用，但其释放机制尚不清楚。三磷酸肌醇（IP 3）受体是钙释放通道，其在细胞生长、发育、感觉感知、神经元信号传导和分泌中具有生理作用。在嗅觉系统中，IP 3受体亚型3（IP 3R 3）仅在微绒毛细胞亚型中表达，微绒毛细胞亚型是表达神经营养因子神经肽Y（NPY）的主要细胞。我们假设，IP 3R 3表达微绒毛细胞分泌足够的神经肽Y需要的神经元群体的持续维护和损伤后的神经再生。我们通过评估野生型、IP 3R 3 +/−和IP 3R 3 −/−小鼠的NPY释放和再生能力来解决这个问题。损伤，使用细胞外ATP模拟，诱导IP 3受体介导的野生型小鼠的NPY释放。在IP 3R 3 −/−小鼠中，ATP诱发的NPY释放受损，表明IP 3R 3有助于损伤后的NPY释放。在正常的生理条件下，IP 3R 3 −/−小鼠和这些小鼠的外植体都有较少的祖细胞增殖和分化成未成熟的神经元。虽然成熟神经元的数量和体内增殖率没有改变，但在IP 3R 3 −/−小鼠的嗅上皮中，对嗅觉毒性物质satratoxin G和嗅球消融损伤的增殖反应受到损害。IP 3R 3 −/−小鼠中NPY释放和祖细胞数量的减少表明IP 3R 3在组织稳态和神经再生中的作用。总的来说，这些数据表明表达IP 3R 3的微绒毛细胞对损伤有积极的反应并促进恢复。
Calcium-dependent release of neurotrophic factors plays an important role in the maintenance of neurons, yet the release mechanisms are understudied. The inositol triphosphate (IP3) receptor is a calcium release channel that has a physiological role in cell growth, development, sensory perception, neuronal signaling and secretion. In the olfactory system, the IP3 receptor subtype 3 (IP3R3) is expressed exclusively in a microvillous cell subtype that is the predominant cell expressing neurotrophic factor neuropeptide Y (NPY). We hypothesized that IP3R3-expressing microvillous cells secrete sufficient NPY needed for both the continual maintenance of the neuronal population and for neuroregeneration following injury. We addressed this question by assessing the release of NPY and the regenerative capabilities of wild type, IP3R3+/−, and IP3R3−/− mice. Injury, simulated using extracellular ATP, induced IP3 receptor-mediated NPY release in wild-type mice. ATP-evoked NPY release was impaired in IP3R3−/− mice, suggesting that IP3R3 contributes to NPY release following injury. Under normal physiological conditions, both IP3R3−/− mice and explants from these mice had fewer progenitor cells that proliferate and differentiate into immature neurons. Although the number of mature neurons and the in vivo rate of proliferation were not altered, the proliferative response to the olfactotoxicant satratoxin G and olfactory bulb ablation injury was compromised in the olfactory epithelium of IP3R3−/− mice. The reductions in both NPY release and number of progenitor cells in IP3R3−/− mice point to a role of the IP3R3 in tissue homeostasis and neuroregeneration. Collectively, these data suggest that IP3R3 expressing microvillous cells are actively responsive to injury and promote recovery.
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影响因子：
3.3
作者：
Jia, C.;Doherty, J. P.;Crudgington, S.;Hegg, C. C.
通讯作者：
Hegg, C. C.
影响因子：
3.5
作者：
Jia, Cuihong;Hegg, Colleen Cosgrove
通讯作者：
Hegg, Colleen Cosgrove
影响因子：
4.7
作者：
Fang, Kuan-Min;Yang, Chung-Shi;Tzeng, Shun-Fen
通讯作者：
Tzeng, Shun-Fen
影响因子：
3.4
作者：
Fukuda, Nanaho;Shirasu, Mika;Mikoshiba, Katsuhiko
通讯作者：
Mikoshiba, Katsuhiko
影响因子：
6.1
作者：
Jia C;Hegg CC
通讯作者：
Hegg CC