BMP7 retards peripheral myelination by activating p38 MAPK in Schwann cells
BMP7 retards peripheral myelination by activating p38 MAPK in Schwann cells
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BMP7 通过激活雪旺细胞中的 p38 MAPK 延迟外周髓鞘形成
DOI：
10.1038/srep31049
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发表时间：
2016-08-05
影响因子：
4.6
通讯作者：
Sun, Cheng
中科院分区：
文献类型：
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作者：
Liu, Xiaoyu;Zhao, Yahong;Sun, Cheng
雪旺细胞（SC）髓鞘形成是神经系统正常生理功能的关键，但其潜在的分子机制仍不太清楚。在这里，我们发现，骨形态发生蛋白7（BMP 7）的表达与髓鞘基因表达呈负相关，在外周髓鞘形成，这表明，BMP 7可能是髓鞘基因表达的负调节。我们的实验进一步表明，BMP 7的应用减弱了cAMP诱导的SC中髓鞘基因的表达。下游通路分析表明，P38 MAPK和SMAD都被外源性BMP 7激活。药物干预和基因沉默研究表明，p38 MAPK，而不是SMAD，是负责BMP 7介导的髓鞘基因表达抑制。此外，BMP 7可上调c-Jun（一种潜在的外周髓鞘形成负调控因子）的表达。总之，我们的研究结果表明，BMP 7是外周髓鞘基因表达的负调控因子，p38 MAPK/c-Jun轴可能是BMP 7在此过程中的主要下游靶点。
Schwann cell (SC) myelination is pivotal for the proper physiological functioning of the nervous system, but the underlying molecular mechanism remains less well understood. Here, we showed that the expression of bone morphogenetic protein 7 (BMP7) inversely correlates with myelin gene expression during peripheral myelination, which suggests that BMP7 is likely a negative regulator for myelin gene expression. Our experiments further showed that the application of BMP7 attenuates the cAMP induced myelin gene expression in SCs. Downstream pathway analysis suggested that both p38 MAPK and SMAD are activated by exogenous BMP7 in SCs. The pharmacological intervention and gene silence studies revealed that p38 MAPK, not SMAD, is responsible for BMP7-mediated suppression of myelin gene expression. In addition, c-Jun, a potential negative regulator for peripheral myelination, was up-regulated by BMP7.In vivoexperiments showed that BMP7 treatment greatly impaired peripheral myelination in newborn rats. Together, our results established that BMP7 is a negative regulator for peripheral myelin gene expression and that p38 MAPK/c-Jun axis might be the main downstream target of BMP7 in this process.