Mechanical Strain Promotes Proliferation of Adipose-Derived Stem Cells Through the Integrin β1-Mediated RhoA/Myosin Light Chain Pathway
Mechanical Strain Promotes Proliferation of Adipose-Derived Stem Cells Through the Integrin β1-Mediated RhoA/Myosin Light Chain Pathway
复制标题
机械应变通过整合素 beta 1 介导的 RhoA/肌球蛋白轻链途径促进脂肪干细胞增殖
DOI：
10.1089/ten.tea.2019.0266
复制
发表时间：
2020-03-19
影响因子：
4.1
通讯作者：
Yuan, Yi
中科院分区：
文献类型：
--
作者：
Chen, Xihang;Deng, Zilong;Yuan, Yi
在脂肪组织再生过程中，外部体积扩张（EVE）促进脂肪源性干细胞（ADSCs）的增殖。然而，EVE被翻译成生化信号并随后诱导ADSCs增殖的机制尚不清楚。在此，我们研究了大鼠脂肪组织中的菌株和EVE的机械化学信号。此外，使用定制的Flexcell装置评估机械应变对ADSCs增殖的影响。脂肪组织的应变水平在第1周达到峰值，然后随着时间的推移而下降，细胞增殖率也受到类似的影响。整合素β 1和RhoA/肌球蛋白轻链（MLC）途径的机械菌株依赖性激活参与细胞增殖。12%机械应变下ADSCs的体外增殖率高于6%和0%机械应变下的增殖率。整合素β 1的机械应变依赖性激活促进了小GTPase RhoA的激活和MLC的磷酸化。此外，整合素β 1的敲低降低了RhoA/MLC通路的激活和ADSCs对机械应变的增殖。综上所述，本研究首次提供了机械化学信号响应EVE的证据。这些数据可能有助于阐明不同应变水平对脂肪组织再生的影响。影响声明外部体积扩张（EVE）诱导脂肪组织再生，在纠正软组织缺陷方面具有巨大的治疗潜力。本研究表明，EVE通过激活整合素β 1及其关键的下游信号分子，即小GTPase RhoA和p-肌球蛋白轻链，促进脂肪源性干细胞的增殖。本研究结果可辅助组织工程的临床应用，为脂肪组织再生的临床调控提供新的思路。
External volume expansion (EVE) promotes proliferation of adipose-derived stem cells (ADSCs) during adipose tissue regeneration. However, the mechanism by which EVE is translated into biochemical signals and subsequently induces proliferation of ADSCs is poorly understood. Here, we investigated the strain in adipose tissue and mechanochemical signaling upon EVE in rats. In addition, the effect of mechanical strain on proliferation of ADSCs was assessed using a custom-built Flexcell device. The level of strain in adipose tissue upon EVE peaked at week 1 and then decreased over time, and the cell proliferation rate was similarly affected. Mechanical strain-dependent activation of integrin beta 1 and the RhoA/myosin light chain (MLC) pathway was involved in cell proliferation. The proliferation rate of ADSCs was higher under 12% mechanical strain than under 6% and 0% mechanical strain in vitro. Mechanical strain-dependent activation of integrin beta 1 promoted activation of the small GTPase RhoA and phosphorylation of MLC. Furthermore, knockdown of integrin beta 1 attenuated activation of the RhoA/MLC pathway and proliferation of ADSCs in response to mechanical strain. Taken together, this study provides the first evidence of mechanochemical signaling in response to EVE. These data may help elucidate the effects of different strain levels on adipose tissue regeneration.Impact statementExternal volume expansion (EVE) induces adipose tissue regeneration and has great therapeutic potential to correct soft tissue defects. This study showed that EVE promotes proliferation of adipose-derived stem cells by activating integrin beta 1 and its crucial downstream signaling molecules, namely the small GTPase RhoA and p-myosin light chain. The findings of this study may assist clinical tissue engineering applications and provide new insights into the regulation of adipose tissue regeneration in clinical practice.