The Trk family of neurotrophin receptors is downregulated in the lumbar spines of rats with congenital kyphoscoliosis.
The Trk family of neurotrophin receptors is downregulated in the lumbar spines of rats with congenital kyphoscoliosis.
复制标题
神经营养素受体 Trk 家族在先天性脊柱后侧凸大鼠的腰椎中表达下调。
DOI：
10.1007/s11010-015-2603-z
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发表时间：
2016
影响因子：
4.3
通讯作者：
Koibuchi N
中科院分区：
文献类型：
--
作者：
Tsunoda D;Iizuka H;Ichinose T;Iizuka Y;Mieda T;Shimokawa N;Takagishi K;Koibuchi N
先天性脊柱侧弯是一种脊柱弯曲度超出生理正常范围的疾病。先天性脊柱侧弯发病的分子机制已开始被阐明，但与先天性脊柱侧弯相关的基因仍不清楚。在此，我们报告了使用DNA微阵列对先天性脊柱侧凸大鼠模型脊柱中基因表达的全面分析结果。这些大鼠(石桥大鼠，IS)表现出与骨形成相关的基因表达水平降低，如与视黄醇代谢和I型胶原相关的基因。有趣的是，IS大鼠屈曲部位的原肌球蛋白受体激酶(Trks：TrkA、TrkB和TrkC)的表达水平较低，属于神经营养受体酪氨酸激酶家族。此外，这种现象仅在脊柱屈曲部位观察到，而Trks在这些大鼠脊柱其他部位的表达水平是正常的。Trks在mRNA和蛋白水平的表达水平均显著降低。我们还观察到IS大鼠腰椎Trk免疫阳性细胞数低于野生型大鼠。这些结果表明Trks在调节正常骨形成中具有重要作用，并为先天性脊柱侧凸的发病机制提供了分子解释。
Congenital scoliosis is a condition characterized by spinal curvature beyond the physiological norm. The molecular mechanisms underlying the pathogenesis of congenital scoliosis are beginning to be clarified; however, the genes related to congenital scoliosis are still unknown. We herein report the results of a comprehensive analysis of gene expression in the spines from a rat model of congenital kyphoscoliosis obtained using DNA microarrays. The rats (Ishibashi rats, IS) showed decreased expression levels of genes associated with bone formation, such as those associated with retinol metabolism and type I collagen. Interestingly, the flexion sites of the IS rats showed low expression levels of tropomyosin receptor kinases (Trks: TrkA, TrkB, and TrkC), which belong to the neurotrophic receptor tyrosine kinase family. Moreover, this phenomenon was observed only in the flexion sites of the spine, and the expression levels of Trks in other parts of the spine in these rats were normal. The decreased expression levels of Trks were observed at both the mRNA and protein levels. We also observed that the number of Trk-immunopositive cells in the lumbar spine in the IS rats was lower than that in wild-type rats. These findings indicate that the Trks have an important function in regulating normal bone formation, and provide a molecular explanation for the pathogenesis of congenital kyphoscoliosis.