Mihalko Emily P, Brown Ashley C
Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina at Chapel Hill, Raleigh, North Carolina 27695, United States.
Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27695, United States.
ACS Biomater Sci Eng. 2018 Apr 9;4(4):1149-1161. doi: 10.1021/acsbiomaterials.6b00751. Epub 2017 Apr 19.
Epithelial to mesenchymal transitions (EMT) involve the phenotypic change of epithelial cells into fibroblast-like cells. This process is accompanied by the loss of cell-cell contacts, increased extracellular matrix (ECM) production, stress fiber alignment, and an increase in cell mobility. While essential for development and wound repair, EMT has also been recognized as a contributing factor to fibrotic diseases and cancer. Both chemical and mechanical cues, such as tumor necrosis factor alpha, NF-κB, Wnt, Notch, interleukin-8, metalloproteinase-3, ECM proteins, and ECM stiffness can determine the degree and duration of EMT events. Additionally, transforming growth factor beta is a primary driver of EMT and, interestingly, can be activated through cell-mediated mechanoactivation. In this review, we highlight recent findings demonstrating the contribution of mechanical stimuli, such as tissue and material stiffness, in driving EMT. We then highlight material strategies for controlling EMT events. Finally, we discuss drivers of the similar process of endothelial to mesenchymal transition (EndoMT) and corresponding material strategies for controlling EndoMT.
上皮-间质转化（EMT）涉及上皮细胞向成纤维细胞样细胞的表型转变。这一过程伴随着细胞间接触的丧失、细胞外基质（ECM）产生增加、应力纤维排列以及细胞迁移能力增强。虽然EMT对发育和伤口修复至关重要，但它也被认为是导致纤维化疾病和癌症的一个因素。化学和机械信号，如肿瘤坏死因子α、核因子κB、Wnt、Notch、白细胞介素-8、金属蛋白酶-3、ECM蛋白和ECM硬度，都可以决定EMT事件的程度和持续时间。此外，转化生长因子β是EMT的主要驱动因素，有趣的是，它可以通过细胞介导的机械激活而被激活。在这篇综述中，我们重点介绍了最近的研究结果，这些结果证明了机械刺激，如组织和材料硬度，在驱动EMT中的作用。然后我们重点介绍了控制EMT事件的材料策略。最后，我们讨论了内皮-间质转化（EndoMT）类似过程的驱动因素以及控制EndoMT的相应材料策略。
