Anisotropic regulation of Ankrd2 gene expression in skeletal muscle by mechanical stretch.
Anisotropic regulation of Ankrd2 gene expression in skeletal muscle by mechanical stretch.
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通过机械拉伸对骨骼肌中 Ankrd2 基因表达的各向异性调节。
DOI：
10.1096/fj.10-158386
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Boriek,AladinM
中科院分区：
文献类型：
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作者：
Mohamed,JunaithS;Lopez,MichaelA;Cox,GregoryA;Boriek,AladinM
在体内，横膈膜肌肉在肌纤维的方向上和在纤维的横向上都受到机械力。然而，定向机械力在骨骼肌基因调控中的作用完全未知。在这里，我们确定了在横膈膜肌纤维的纵向和横向拉伸上调Ankrd 2基因表达的两个不同的信号通路在野生型（WT）和mdm，一个小鼠模型的肌营养不良症与早发性进行性肌肉萎缩。纵向拉伸激活NF-κB和AP-1转录因子，而横向拉伸仅激活AP-1转录因子。有趣的是，纵向拉伸仅通过NF-κB激活Ankrd 2启动子，而横向拉伸通过AP-1激活Ankrd 2启动子。此外，我们发现纵向牵张激活Akt，Akt通过NF-κB上调Ankrd 2的表达。然而，横向拉伸激活Ras-GTP，Raf-1和Erk 1/2蛋白，其通过AP-1上调Ankrd 2表达。令人惊讶的是，牵张激活的NF-κB和AP-1信号通路在基础水平上不参与Ankrd 2的调节，这在mdm小鼠膈肌中是高的。综上所述，我们的数据显示了通过两种不同的机械敏感信号通路在WT和MDM小鼠的膈肌中对Ankrd 2基因表达的各向异性调节。Mohamed，J.S.，洛佩斯，M.一、考克斯，G.一、Boriek，A. M.机械牵张对骨骼肌Ankrd 2基因表达的各向异性调控
The diaphragm muscles in vivo are subjected to mechanical forces both in the direction of the muscle fibers and in the direction transverse to the fibers. However, the effect of directional mechanical forces in skeletal muscle gene regulation is completely unknown. Here, we identified that stretch in the longitudinal and transverse directions to the diaphragm muscle fibers up-regulated Ankrd2 gene expression by two distinct signaling pathways in wild-type (WT) and mdm, a mouse model of muscular dystrophy with early-onset of progressive muscle-wasting. Stretch in the longitudinal direction activated both NF-κB and AP-1 transcription factors, whereas stretch in the transverse direction activated only AP-1 transcription factor. Interestingly, longitudinal stretch activated Ankrd2 promoter only by NF-κB, whereas transverse stretch activated Ankrd2 promoter by AP-1. Moreover, we found that longitudinal stretch activated Akt, which up-regulated Ankrd2 expression through NF-κB. However, transverse stretch activated Ras-GTP, Raf-1, and Erk1/2 proteins, which up-regulated Ankrd2 expression through AP-1. Surprisingly, the stretch-activated NF-κB and AP-1 signaling pathways was not involved in Ankrd2 regulation at the basal level, which was high in the mdm mouse diaphragm. Taken together, our data show the anisotropic regulation of Ankrd2 gene expression in the diaphragm muscles of WT and mdm mice via two distinct mechanosensitive signaling pathways.—Mohamed, J. S., Lopez, M. A., Cox, G. A., Boriek, A. M. Anisotropic regulation of Ankrd2 gene expression in skeletal muscle by mechanical stretch.