Department of Cell & Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada.
Cells. 2021 Apr 23;10(5):994. doi: 10.3390/cells10050994.
Cells in the human body experience and integrate a wide variety of environmental cues. A growing interest in tissue mechanics in the past four decades has shown that the mechanical properties of tissue drive key biological processes and facilitate disease development. However, tissue stiffness is not only a potent behavioral cue, but also a product of cellular signaling activity. This review explores both roles of tissue stiffness in the context of inflammation and fibrosis, and the important molecular players driving such processes. During inflammation, proinflammatory cytokines upregulate tissue stiffness by increasing hydrostatic pressure, ECM deposition, and ECM remodeling. As the ECM stiffens, cells involved in the immune response employ intricate molecular sensors to probe and alter their mechanical environment, thereby facilitating immune cell recruitment and potentiating the fibrotic phenotype. This powerful feedforward loop raises numerous possibilities for drug development and warrants further investigation into the mechanisms specific to different fibrotic diseases.
人体内的细胞会感知和整合各种环境线索。在过去的四十年中，人们对组织力学越来越感兴趣，研究表明组织的力学特性可以驱动关键的生物学过程并促进疾病的发展。然而，组织硬度不仅是一种有力的行为线索，也是细胞信号活动的产物。本综述探讨了组织硬度在炎症和纤维化背景下的双重作用，以及驱动这些过程的重要分子参与者。在炎症过程中，促炎细胞因子通过增加静水压力、细胞外基质（ECM）沉积和 ECM 重塑来上调组织硬度。随着 ECM 的变硬，参与免疫反应的细胞利用复杂的分子传感器来探测和改变其机械环境，从而促进免疫细胞的募集并增强纤维化表型。这种强大的前馈回路为药物开发提供了许多可能性，并需要进一步研究不同纤维化疾病的特定机制。
