The ability of cells to sense and respond to changes in mechanical environment is vital in conditions of organ injury when the architecture of normal tissues is disturbed or lost. Among the various cellular players that respond to injury, fibroblasts take center stage in re-establishing tissue integrity by secreting and organizing extracellular matrix into stabilizing scar tissue. Activation, activity, survival, and death of scar-forming fibroblasts are tightly controlled by mechanical environment and proper mechanotransduction ensures that fibroblast activities cease after completion of the tissue repair process. Conversely, dysregulated mechanotransduction often results in fibroblast over-activation or persistence beyond the state of normal repair. The resulting pathological accumulation of extracellular matrix is called fibrosis, a condition that has been associated with over 40% of all deaths in the industrialized countries. Consequently, elements in fibroblast mechanotransduction are scrutinized for their suitability as anti-fibrotic therapeutic targets. We review the current knowledge on mechanically relevant factors in the fibroblast extracellular environment, cell-matrix and cell-cell adhesion structures, stretch-activated membrane channels, stress-regulated cytoskeletal structures, and co-transcription factors. We critically discuss the targetability of these elements in therapeutic approaches and their progress in pre-clinical and/or clinical trials to treat organ fibrosis.

当正常组织的结构受到干扰或丧失时，细胞感知和响应机械环境变化的能力在器官损伤的情况下至关重要。在对损伤做出反应的各种细胞参与者中，成纤维细胞通过分泌和组织细胞外基质形成稳定的疤痕组织来重建组织完整性。疤痕形成成纤维细胞的激活、活动、存活和死亡受到机械环境的严格控制，适当的机械转导可确保成纤维细胞活动在组织修复过程完成后停止。相反，机械转导失调通常会导致成纤维细胞过度激活或持续超出正常修复状态。由此产生的细胞外基质病理性积聚称为纤维化，这种疾病与工业化国家 40% 以上的死亡有关。因此，对成纤维细胞机械转导中的元件作为抗纤维化治疗靶点的适用性进行了仔细检查。我们回顾了有关成纤维细胞外环境、细胞基质和细胞间粘附结构、拉伸激活膜通道、应激调节细胞骨架结构和共转录因子中机械相关因素的最新知识。我们批判性地讨论这些元素在治疗方法中的靶向性及其在治疗器官纤维化的临床前和/或临床试验中的进展。