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Role of oncostatin M in the nervous systems

制瘤素 M 在神经系统中的作用

基本信息

批准号：
15500264
负责人：
MORIKAWA Yoshihiro
金额：
$ 2.43万
依托单位：
Wakayama Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15500264/
关键词：
oncostatin M nociception dorsal root ganglia neuron TRPV1 P2X3 TRPV2 TrkC VR1

项目摘要

Oncostatin M(OSM) is a member of the interleukin(IL)-6 cytokine family, which is involved in definitive hematopoiesis, the development of liver, and local inflammation. However, little is known about the role of OSM in the nervous system. In situ hybridization shows that OSM receptor β (OSMR) mRNA was found in astrocytes of olfactory bulb, epithelial cells of choroid plexus, and meningeal cells in pia mater. Its gene expression was first observed in large neurons of the hypoglossal nucleus at embryonic day (E) 14.5, which was sustained until neonatal mice. OSMR mRNA and protein were mainly localized in the ventral subnucleus of the developing hypoglossal nucleus.In the adult dorsal root ganglia (DRGs), OSMR was exclusively expressed in small-sized neurons. Approximately 28% of OSMR-positive neurons contained TrkA-immunoreactivity (-ir), 63% expressed Ret-ir. No neuropeptides, including substance P and calcitonin gene-related peptide, were contained in the neurons. Furthermore, all OSMR-positive neurons expressed both vanilloid receptor 1(TRPV1) and P2X3 purinergic receptor.In the DRGs of the OSM-deficient mice, TRPV1- and P2X3-positive small-sized neurons were significantly decreased. OSM-deficient mice displayed significantly reduced noxious responses in models of acute thermal, mechanical, chemical, and visceral pain. Thus, OSM plays an essential role in the development of a subtype of nociceptive neurons in the DRGs.Little is known about the neurotrophin dependence of TRPV2-positive neurons in the developing and adult DRGs of mice. TRPV2 was. first expressed in DRG neurons at E 11.5, when neither TRPV1 nor TRPM8 were detected yet. TrkC was expressed in most of TRPV2-positive DRG neurons at E11.5 and E13.5. In adult DRGs, TrkC and Ret were expressed in 68% and 25% of TRPV2-positive neurons, respectively. These results suggest that TRPV2 is expressed predominantly in the NT-3-dependent subpopulation of DRG neurons throughout the development and in adult mice.

抑瘤素M（Oncostatin M，OSM）是白细胞介素（IL）-6细胞因子家族的成员，参与造血、肝脏发育和局部炎症反应。然而，关于OSM在神经系统中的作用知之甚少。原位杂交结果显示OSM受体β（OSMR）mRNA主要表达于嗅球星形胶质细胞、脉络丛上皮细胞和软脑膜脑膜细胞。其基因表达首先在胚胎第14.5天（E）的舌下神经核的大神经元中观察到，该表达持续到新生小鼠。OSMR mRNA和蛋白主要定位于发育中的舌下神经核腹侧亚核，在成年后的背根神经节（dorsal root ganglia，DRG）中，OSMR仅表达于小型神经元。OSMR阳性神经元中约28%表达TrkA免疫反应（-ir），63%表达Ret-ir，不含P物质和降钙素基因相关肽等神经肽。OSM缺陷小鼠背根神经节中TRPV 1和P2 X3阳性的小神经元数量明显减少。在急性热、机械、化学和内脏疼痛模型中，OSM缺陷小鼠显示出显著降低的伤害性反应。因此，OSM在DRGs伤害感受神经元亚型的发育中起重要作用。TRPV 2是。在E11.5，TRPV 1和TRPM 8均未被检测到时，在DRG神经元中首次表达。在E11.5和E13.5，TrkC在大多数TRPV 2阳性DRG神经元中表达。在成年DRG中，TrkC和Ret分别在68%和25%的TRPV 2阳性神经元中表达。这些结果表明，TRPV 2主要表达在整个发育过程中和成年小鼠的DRG神经元的NT-3依赖性亚群中。