The preservation of tissue and organ architecture and function depends on tightly regulated interactions of cells with the extracellular matrix (ECM). These interactions are maintained in a dynamic equilibrium that balances intracellular, myosin-generated tension with extracellular resistance conferred by the mechanical properties of the extracellular matrix. Disturbances of this equilibrium can lead to the development of fibrotic lesions that are associated with a wide repertoire of high prevalence diseases including obstructive cardiovascular diseases, muscular dystrophy and cancer. Mechanotransduction is the process by which mechanical cues are converted into biochemical signals. At the core of mechanotransduction are sensory systems, which are frequently located at sites of cell-ECM and cell-cell contacts. As integrins (cell-ECM junctions) and cadherins (cell-cell contacts) have been extensively studied, we focus here on the properties of the discoidin domain receptor 1 (DDR1), a tyrosine kinase that mediates cell adhesion to collagen. DDR1 expression is positively associated with fibrotic lesions of heart, kidney, liver, lung and perivascular tissues. As the most common end-point of all fibrotic disorders is dysregulated collagen remodeling, we consider here the mechanical signaling functions of DDR1 in processing of fibrillar collagen that lead to tissue fibrosis.

中文翻译：

---

通过盘状结构域受体 1 的机械信号传导在组织纤维化中发挥着核心作用。

组织和器官结构和功能的保存取决于细胞与细胞外基质 (ECM) 的严格调节的相互作用。这些相互作用保持动态平衡，平衡细胞内肌球蛋白产生的张力与细胞外基质机械特性赋予的细胞外阻力。这种平衡的紊乱可能导致纤维化病变的发展，而纤维化病变与多种高患病率疾病相关，包括阻塞性心血管疾病、肌肉萎缩症和癌症。机械转导是将机械信号转化为生化信号的过程。机械转导的核心是感觉系统，通常位于细胞-ECM 和细胞-细胞接触的部位。由于整合素（细胞-ECM 连接）和钙粘蛋白（细胞-细胞接触）已被广泛研究，我们在此重点关注盘状结构域受体 1 (DDR1) 的特性，这是一种介导细胞与胶原蛋白粘附的酪氨酸激酶。DDR1表达与心脏、肾脏、肝脏、肺和血管周围组织的纤维化病变呈正相关。由于所有纤维化疾病最常见的终点是胶原蛋白重塑失调，因此我们在这里考虑 DDR1 在导致组织纤维化的纤维状胶原蛋白处理过程中的机械信号传导功能。