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首页> 外文期刊>Journal of tissue engineering and regenerative medicine >The effect of mechanical stress on the proliferation, adipogenic differentiation and gene expression of human adipose-derived stem cells
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The effect of mechanical stress on the proliferation, adipogenic differentiation and gene expression of human adipose-derived stem cells

机译：机械胁迫对人脂肪衍生干细胞增殖，脂肪发生分化和基因表达的影响

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摘要

To allow for a better implementation of external volume expansion to clinical applications for soft tissue regeneration, it is necessary to comprehensively understand the underlying mechanisms. As human adipose-derived stem cells (hASCs) play a crucial role in soft tissue enlargement, we investigated the impact of cyclic stretch on gene expression, proliferation rate and adipogenic differentiation of these cells. After cyclic stretching, RNA was extracted and subjected to DNA microarray analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Also, the expression of FABP4 mRNA was analysed by RT-qPCR to test whether mechanical stretch affected adipogenic differentiation of hASCs. The proliferation rate was assessed using the alamarBlue assay and Ki-67 staining. A cell cycle analysis was performed with flow cytometry and Western blot. We found that cyclic stretch significantly induced the expression of CYP1B1 mRNA. Furthermore, the adipogenic differentiation of hASCs was impaired, as was the proliferation. This was partly due to a decrease in extracellular signal-regulated kinase (ERK) 1/2 and histone H3 phosphorylation, suggesting a growth arrest in the G(2)/M phase of the cell cycle. Enrichment analyses demonstrated that stretch-regulated genes were over-represented in pathways and biological processes involved in extracellular matrix organization, vascular remodelling and responses to cell stress. Taken together, mechanical stress impaired both proliferation and adipogenic differentiation, but led to a tissue-remodelling phenotype of hASCs. These data suggest that extracellular matrix remodelling and neoangiogenesis may play a more important role in external volume expansion than proliferation and adipogenesis of hASCs. Copyright (C) 2017 John Wiley & Sons, Ltd.
机译：为了更好地实现外部体积扩展至软组织再生的临床应用，必须全面了解潜在的机制。随着人脂肪衍生的干细胞（HASC）在软组织扩大中发挥至关重要的作用，我们研究了循环伸展对这些细胞的基因表达，增殖率和脂肪切分化的影响。循环拉伸后，提取RNA并进行DNA微阵列分析和逆转录定量聚合酶链反应（RT-QPCR）。此外，通过RT-QPCR分析Fabp4 mRNA的表达，以测试机械拉伸是否影响了HASC的脂肪生成分化。使用Alamarblue测定和Ki-67染色评估增殖率。用流式细胞术和Western印迹进行细胞循环分析。我们发现循环延伸显着诱导CYP1B1 mRNA的表达。此外，哈布斯的脂肪生成分化损害，同样的增殖也是如此。这部分是由于细胞外信号调节激酶（ERK）1/2和组蛋白H3磷酸化的降低，表明细胞周期的G（2）/ m相中的生长停滞。富集分析证明，在细胞外基质组织，血管重塑和对细胞应激的反应中参与的途径和生物过程中含有伸缩稳压基因。一起携带机械应力损害增殖和脂肪发生分化，但导致了HASC的组织重塑表型。这些数据表明细胞外基质重塑和新谐振发生在外部体积膨胀中可能比HASC的增殖和脂肪发生在外部体积膨胀中发挥更重要的作用。版权所有（C）2017 John Wiley＆Sons，Ltd。

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