The retinol‐retinoic acid metabolic pathway is impaired in the lumbar spine of a rat model of congenital kyphoscoliosis
The retinol‐retinoic acid metabolic pathway is impaired in the lumbar spine of a rat model of congenital kyphoscoliosis
复制标题
先天性脊柱后侧凸大鼠模型腰椎中视黄醇-视黄酸代谢途径受损
DOI：
10.1002/jcb.28762
复制
发表时间：
2019
影响因子：
4
通讯作者：
N. Shimokawa
中科院分区：
文献类型：
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作者：
Hiroyuki Sonoda;Haku Iizuka;S. Ishiwata;Daisuke Tsunoda;Masako Abe;K. Takagishi;H. Chikuda;N. Koibuchi;N. Shimokawa
虽然先天性脊柱侧凸被定义为一种遗传性疾病，其特征是脊柱的先天性和异常曲度，但我们对这种疾病的遗传基础的了解还不够。在此，我们证明视黄醇-维甲酸代谢途径的下调参与了先天性脊柱侧弯的发病。通过分析DNA微阵列数据，我们发现与视黄醇代谢途径相关的基因在石桥大鼠(IS)腰椎中的表达水平降低。IS是一种先天性脊柱后凸大鼠模型。在这一途径中，将视黄醇转化为视黄酸的两种酶Adh1和Aldh1a2的表达在基因和蛋白质水平上都降低了。位于该途径下游的维甲酸受体α和骨形态发生蛋白2在骨形成中起核心作用，其表达也下调。有趣的是，IS大鼠的血清视黄醇水平高于野生型对照大鼠。这些结果表明，视黄醇到视黄酸的充分转化对正常骨形成的调节非常重要，也可能是了解先天性脊柱侧弯发病机制的关键因素。
Although congenital scoliosis is defined as a genetic disease characterized by a congenital and abnormal curvature of the spinal vertebrae, our knowledge of the genetic underpinnings of the disease is insufficient. We herein show that the downregulation of the retinol‐retinoic acid metabolism pathway is involved in the pathogenesis of congenital scoliosis. By analyzing DNA microarray data, we found that the expression levels of genes associated with the retinol metabolism pathway were decreased in the lumbar spine of Ishibashi rats (IS), a rat model of congenital kyphoscoliosis. The expression of Adh1 and Aldh1a2 (alcohol dehydrogenase), two enzymes that convert retinol to retinoic acid in this pathway, were decreased at both the gene and protein levels. Rarα, a receptor of retinoic acid and bone morphogenetic protein 2, which play a central role in bone formation and are located downstream of this pathway, were also downregulated. Interestingly, the serum retinol levels of IS rats were higher than those of wild‐type control rats. These results indicate that the adequate conversion from retinol to retinoic acid is extremely important in the regulation of normal bone formation and it may also be a key factor for understanding the pathogenesis of congenital scoliosis.
DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
E A Snell;R. F. Furlong;P. W. H. Holland;B F Lang;C. O 'kelly;T. Nerad;M. W. Gray;G. Burger-G.-B
通讯作者：
E A Snell;R. F. Furlong;P. W. H. Holland;B F Lang;C. O 'kelly;T. Nerad;M. W. Gray;G. Burger-G.-B
受体选择性视黄醇表明视黄酸受体α和γ参与F9胚胎癌细胞中bmp-2和bmp-4的调节。
DOI：
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发表时间：
1996
期刊：
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
影响因子：
--
作者：
Rogers,MB
通讯作者：
Rogers,MB
影响因子：
3.5
作者：
Amengual, Jaume;Zhang, Ning;Von Lintig, Johannes
通讯作者：
Von Lintig, Johannes