Mechanical-stretch of C2C12 myoblasts inhibits expression of Toll-like receptor 3 (TLR3) and of autoantigens associated with inflammatory myopathies.
Mechanical-stretch of C2C12 myoblasts inhibits expression of Toll-like receptor 3 (TLR3) and of autoantigens associated with inflammatory myopathies.
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C2C12 成肌细胞的机械拉伸抑制 Toll 样受体 3 (TLR3) 和与炎症性肌病相关的自身抗原的表达
DOI：
10.1371/journal.pone.0079930
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Liao H
中科院分区：
文献类型：
--
作者：
Chen R;Feng L;Ruan M;Liu X;Adriouch S;Liao H
最近对炎症性自身免疫性肌病患者的研究表明，适度的运动训练可以改善或至少稳定肌肉力量和功能，而不会导致疾病flARES。然而，这种有益作用的确切机制还没有被广泛研究。在这里，我们使用一个体外拉伸的C2C12成肌细胞模型来研究机械拉伸是否会影响成肌细胞的增殖或促炎基因的表达。我们的结果表明，周期性机械拉伸刺激了C2C12细胞周期和肌肉中与机械拉伸途径相关的分子(钙调素、nNOS、基质金属蛋白酶-2、肝细胞生长因子和c-蛋氨酸)的早期上调。出乎意料的是，机械拉伸还减少了TLR3和炎症性自身免疫性肌病(Mi-2，HRS，DNA-PKcs，U1-70)中代表自身抗原的蛋白质的表达。有趣的是，体外刺激或抑制CaM、NOS、HGF或c-Met分子会影响自身抗原和TLR3蛋白的表达，证实了它们在机械拉伸过程中抑制自身抗原和TLR3的作用。总体而言，这项研究首次证明了机械拉伸可以通过减少肌肉自身抗原和促炎TLR3的表达而受益，并可能为理解阻力训练如何减少与肌炎相关的症状提供新的见解。
Recent studies in patients suffering from inflammatory autoimmune myopathies suggested that moderate exercise training improves or at least stabilizes muscle strength and function without inducing disease flares. However, the precise mechanisms involved in this beneficial effect have not been extensively studied. Here we used a model of in vitro stretched C2C12 myoblasts to investigate whether mechanical stretch could influence myoblast proliferation or the expression of proinflammatory genes. Our results demonstrated that cyclic mechanical stretch stimulated C2C12 cell cycling and early up-regulation of the molecules related to mechanical-stretch pathway in muscle (calmodulin, nNOS, MMP-2, HGF and c-Met). Unexpectedly, mechanical stretch also reduced the expression of TLR3 and of proteins known to represent autoantigens in inflammatory autoimmune myopathies (Mi-2, HRS, DNA-PKcs, U1-70). Interestingly, stimulation or inhibition of calmodulin, NOS, HGF or c-Met molecules in vitro affected the expression of autoantigens and TLR3 proteins confirming their role in the inhibition of autoantigens and TLR3 during mechanical stretch. Overall, this study demonstrates for the first time that mechanical stretch could be beneficial by reducing expression of muscle autoantigens and of pro-inflammatory TLR3 and may provide new insight to understand how resistance training can reduce the symptoms associated with myositis.
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影响因子：
--
作者：
Tournadre, A.;Lenief, V.;Miossec, P.
通讯作者：
Miossec, P.
影响因子：
15.9
作者：
Kuroiwa, T;Kakishita, E;Iwasaki, T
通讯作者：
Iwasaki, T
影响因子：
2
作者：
Tatsumi, R.;Hattori, A.;Ito, T.
通讯作者：
Ito, T.
影响因子：
4
作者：
Zhan, Mei;Jin, Bingwen;Li, Yi-Ping
通讯作者：
Li, Yi-Ping
影响因子：
5.5
作者：
Tatsumi, Ryuichi;Wuollet, Adam L.;Allen, Ronald E.
通讯作者：
Allen, Ronald E.