Pathological remodeling of the extracellular matrix (ECM) by activated myofibroblasts is a hallmark of fibrotic diseases and desmoplastic tumors. Activation of myofibroblasts occurs in response to fibrogenic tissue injury as well as in tumor-associated fibrotic reactions. The molecular determinants of myofibroblast activation in fibrosis and tumor stroma have traditionally been viewed to include biochemical agents, such as dysregulated growth factor and cytokine signaling, which profoundly alter the biology of fibroblasts, ultimately leading to overexuberant matrix deposition and fibrosis. More recently, compelling evidence has shown that altered mechanical properties of the ECM such as matrix stiffness are major drivers of tissue fibrogenesis by promoting mechano-activation of fibroblasts. In this Review, we discuss new insights into the role of the biophysical microenvironment in the amplified activation of fibrogenic myofibroblasts during the development and progression of fibrotic diseases and desmoplastic tumors. We also summarize novel therapeutic targets for anti-fibrotic therapy based on the mechanobiology of tissue fibrosis and tumor stroma, a class of drugs known as "mechano-therapeutics".

中文翻译：

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机械疗法：靶向纤维化和肿瘤基质中的机械信号。

活化的肌成纤维细胞对细胞外基质 (ECM) 的病理性重塑是纤维化疾病和促纤维增生性肿瘤的标志。肌成纤维细胞的激活响应于纤维化组织损伤以及肿瘤相关的纤维化反应。纤维化和肿瘤基质中肌成纤维细胞活化的分子决定因素传统上被认为包括生化因子，例如失调的生长因子和细胞因子信号传导，它们深刻地改变成纤维细胞的生物学，最终导致过度旺盛的基质沉积和纤维化。最近，令人信服的证据表明，通过促进成纤维细胞的机械活化，ECM 机械特性的改变（如基质刚度）是组织纤维化的主要驱动因素。在本次审查中，我们讨论了生物物理微环境在纤维化疾病和促纤维增生性肿瘤的发展和进展过程中纤维化肌成纤维细胞的放大激活中的作用的新见解。我们还总结了基于组织纤维化和肿瘤基质力学生物学的抗纤维化治疗的新治疗靶点，这是一类被称为“机械疗法”的药物。