Long Yi, Niu Yudi, Liang Kaini, Du Yanan
Department of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China; Joint Graduate Program of Peking-Tsinghua-National Institute of Biological Science, Tsinghua University, Beijing, 100084, China.
Department of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China.
Trends Cell Biol. 2022 Jan;32(1):70-90. doi: 10.1016/j.tcb.2021.10.002. Epub 2021 Nov 19.
Mechanical hallmarks of fibrotic microenvironments are both outcomes and causes of fibrosis progression. Understanding how cells sense and transmit mechanical cues in the interplay with extracellular matrix (ECM) and hemodynamic forces is a significant challenge. Recent advances highlight the evolvement of intracellular mechanotransduction pathways responding to ECM remodeling and abnormal hemodynamics (i.e., low and disturbed shear stress, pathological stretch, and increased pressure), which are prevalent biomechanical characteristics of fibrosis in multiple organs (e.g., liver, lung, and heart). Here, we envisage the mechanical communication in cell-ECM, cell-hemodynamics and cell-ECM-cell crosstalk (namely paratensile signaling) during fibrosis expansion. We also provide a comprehensive overview of in vitro and in silico engineering systems for disease modeling that will aid the identification and prediction of mechano-based therapeutic targets to ameliorate fibrosis progression.
纤维化微环境的力学特征既是纤维化进展的结果，也是其原因。了解细胞如何在与细胞外基质（ECM）和血流动力学力的相互作用中感知和传递力学信号是一项重大挑战。最近的进展突出了细胞内机械转导途径的演变，这些途径对ECM重塑和异常血流动力学（即低剪切应力和紊乱剪切应力、病理性拉伸和压力增加）作出反应，而这些是多个器官（如肝脏、肺和心脏）纤维化普遍存在的生物力学特征。在此，我们设想了纤维化扩展过程中细胞-ECM、细胞-血流动力学和细胞-ECM-细胞间串扰（即旁张应力信号传导）中的力学通讯。我们还全面概述了用于疾病建模的体外和计算机工程系统，这将有助于识别和预测基于力学的治疗靶点，以改善纤维化进展。
