Conversion of mechanical force into TGF-β-mediated biochemical signals.
Conversion of mechanical force into TGF-β-mediated biochemical signals.
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DOI：
10.1016/j.cub.2011.04.007
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发表时间：
2011-06-07
期刊：
影响因子：
9.2
通讯作者：
Sakai, Takao
中科院分区：
文献类型：
--
作者：
Maeda, Toru;Sakabe, Tomoya;Sunaga, Ataru;Sakai, Keiko;Rivera, Alexander L.;Keene, Douglas R.;Sasaki, Takako;Stavnezer, Edward;Iannotti, Joseph;Schweitzer, Ronen;Ilic, Dusko;Baskaran, Harihara;Sakai, Takao
机械力影响几乎每一个组织的内稳态。肌腱，不断暴露在可变的机械力下，是研究机械刺激转化为生化反应的一个很好的模型。我们在急性肌腱损伤小鼠模型和体外实验中发现，物理力可以调节细胞外基质（ECM）中活性转化生长因子(TGF)-β的释放。在暴露于不同水平拉伸载荷的组织中检测到的活性TGF-β的数量与物理力的程度直接相关。在生理水平上，机械力通过TGF-β/ smad2 /3介导的信号传导，维持sccleraxis （Scx）的表达，Scx是一种针对细胞及其祖细胞的转录因子。张力负荷的逐渐和暂时丧失会导致Scx表达的可逆性丧失，而突然中断，如横断肌腱损伤，会破坏ECM的结构组织，导致活性TGF-β的过度释放和大量的肌腱细胞死亡，这可以通过TGF-β I型受体抑制剂SD208来预防。我们的研究结果表明，机械力在成人肌腱稳态中起着关键作用。此外，这种机制可以将物理力转化为体内更广泛的组织或系统的生化信号。
Mechanical forces influence homeostasis in virtually every tissue. Tendon, constantly exposed to variable mechanical force, is an excellent model in which to study the conversion of mechanical stimuli into a biochemical response. Here we show in a mouse model of acute tendon injury and in vitro that physical forces regulate the release of active transforming growth factor (TGF)-β from the extracellular matrix (ECM). The quantity of active TGF-β detected in tissue exposed to various levels of tensile loading correlates directly with the extent of physical forces. At physiological levels, mechanical forces maintain, through TGF-β/Smad2/3-mediated signaling, the expression of Scleraxis (Scx), a transcription factor specific for tenocytes and their progenitors. The gradual and temporary loss of tensile loading causes reversible loss of Scx expression, whereas sudden interruption, such as in transection tendon injury, destabilizes the structural organization of the ECM and leads to excessive release of active TGF-β and massive tenocyte death, which can be prevented by the TGF-β type I receptor inhibitor SD208. Our findings demonstrate a critical role for mechanical force in adult tendon homeostasis. Furthermore, this mechanism could translate physical force into biochemical signals in much broader variety of tissues or systems in the body.
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影响因子：
4.8
作者：
Lejard, Veronique;Brideau, Gaelle;Rossert, Jerome
通讯作者：
Rossert, Jerome
影响因子：
16
作者：
Lim, Ssang-Taek;Chen, Xiao Lei;Llic, Dusko
通讯作者：
Llic, Dusko
影响因子：
3.6
作者：
Jinnin, M;Ihn, H;Tamaki, K
通讯作者：
Tamaki, K
影响因子：
2.1
作者：
Banos, Charles C.;Thomas, Amelia H.;Kuo, Catherine K.
通讯作者：
Kuo, Catherine K.
DOI：
10.1126/science.1171643
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Discher DE;Mooney DJ;Zandstra PW
通讯作者：
Zandstra PW