Neuropeptide Y and extracellular signal-regulated kinase mediate injury-induced neuroregeneration in mouse olfactory epithelium.
Neuropeptide Y and extracellular signal-regulated kinase mediate injury-induced neuroregeneration in mouse olfactory epithelium.
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DOI：
10.1016/j.mcn.2011.11.004
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发表时间：
2012-02
影响因子：
3.5
通讯作者：
Hegg, Colleen Cosgrove
中科院分区：
文献类型：
--
作者：
Jia, Cuihong;Hegg, Colleen Cosgrove
关键词：
在嗅上皮（OE）中，损伤诱导ATP释放，随后ATP激活P2嘌呤能受体，通过增加基底祖细胞增殖促进神经再生。atp诱导OE神经再生增加的分子机制尚未确定。本研究探讨了神经增殖因子神经肽Y （NPY）和成纤维细胞生长因子2 （FGF2）以及p44/42细胞外信号调节激酶（ERK）在atp介导的OE神经再生增加中的作用。ATP通过激活P2嘌呤能受体，在体外和体内通过将5 ' -乙基-2 ' -脱氧尿苷（一种胸腺嘧啶类似物）掺入DNA和增殖细胞核抗原（PCNA）蛋白水平来监测OE中基底祖细胞的增殖。ATP诱导球状基底细胞（GBC）激活p44/42 ERK，但水平基底细胞（HBC）没有。在体外和体内，随着时间的推移，ATP对OE中的p44/42 ERK有差异调节，先是短暂抑制（5-15分钟），然后是激活（30分钟- 1小时）p44/42 ERK。此外，ATP通过诱导基底细胞中NPY的释放和随后NPY Y1受体的激活间接激活OE中的p44/42 ERK。ATP与NPY或FGF2对OE神经再生无协同作用。这些数据显然对嗅觉上皮神经再生的药理学调节有影响。
In the olfactory epithelium (OE), injury induces ATP release, and subsequent activation of P2 purinergic receptors by ATP promotes neuroregeneration by increasing basal progenitor cell proliferation. The molecular mechanisms underlying ATP-induced increases in OE neuroregeneration have not been established. In the present study, the roles of neuroproliferative factors neuropeptide Y (NPY) and fibroblast growth factor2 (FGF2), and p44/42 extracellular signal-regulated kinase (ERK) on ATP-mediated increases of neuroregeneration in the OE were investigated. ATP increased basal progenitor cell proliferation in the OE via activation of P2 purinergic receptors in vitro and in vivo as monitored by incorporation of 5′-ethynyl-2′-deoxyuridine, a thymidine analog, into DNA, and proliferating cell nuclear antigen (PCNA) protein levels. ATP induced p44/42 ERK activation in globose basal cells (GBC) but not horizontal basal cells (HBC). ATP differentially regulated p44/42 ERK over time in the OE both in vitro and in vivo with transient inhibition (5–15 min) followed by activation (30 min – 1 hr) of p44/42 ERK. In addition, ATP indirectly activated p44/42 ERK in the OE via ATP-induced NPY release and subsequent activation of NPY Y1 receptors in the basal cells. There were no synergistic effects of ATP and NPY or FGF2 on OE neuroregeneration. These data clearly have implications for the pharmacological modulation of neuroregeneration in the olfactory epithelium.
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影响因子：
6.2
作者：
Hegg, CC;Lucero, MT
通讯作者：
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