Department of Plastic and Reconstructive Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Tissue Eng Part A. 2020 Sep;26(17-18):939-952. doi: 10.1089/ten.TEA.2019.0266. Epub 2020 Mar 19.
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 β1 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 . Mechanical strain-dependent activation of integrin β1 promoted activation of the small GTPase RhoA and phosphorylation of MLC. Furthermore, knockdown of integrin β1 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 statement External 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 β1 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.
外部体积扩张 (EVE) 在脂肪组织再生过程中促进脂肪来源干细胞 (ADSCs) 的增殖。然而，EVE 如何转化为生化信号，进而诱导 ADSCs 增殖的机制尚不清楚。在这里，我们研究了 EVE 作用于大鼠脂肪组织时的应变和机械化学信号。此外，还使用定制的 Flexcell 设备评估了机械应变对 ADSCs 增殖的影响。EVE 后脂肪组织中的应变水平在第 1 周达到峰值，然后随时间逐渐降低，细胞增殖率也受到类似的影响。整合素 β1 和 RhoA/肌球蛋白轻链 (MLC) 通路的机械应变依赖性激活参与了细胞增殖。ADSCs 在 12%机械应变下的增殖率高于 6%和 0%机械应变。整合素 β1 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 β1 的敲低减弱了机械应变诱导的 RhoA/MLC 通路的激活和 ADSCs 的增殖。综上所述，本研究首次提供了 EVE 反应的机械化学信号的证据。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。
