Zhao Tian, Huang Ye, Zhu Jingfei, Qin Yujie, Wu Hao, Yu Jiaxuan, Zhai Qianwen, Li Shun, Qin Xiang, Wang Dengfeng, Li Tingting, Liu Yiyao
Department of Gynecologic Oncology Sichuan Clinical Research Center for Cancer Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, and School of Life Science and Technology, University of Electronic Science and Technology of China Chengdu P. R. China.
TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province Hospital of Chengdu University of Traditional Chinese Medicine Chengdu P. R. China.
MedComm (2020). 2025 Jul 17;6(8):e70281. doi: 10.1002/mco2.70281. eCollection 2025 Aug.
Extracellular matrix (ECM) is a dynamic, three-dimensional network that provides structural support and regulates key biological processes, including cell adhesion, migration, differentiation, and signal transduction. Its mechanical properties, such as stiffness, topology, and viscoelasticity, are crucial in normal and pathological conditions, influencing cell behavior through mechanotransduction pathways. Dysregulation of ECM is linked to various diseases, making a thorough understanding of its composition and properties essential. This review discusses ECM composition, physical properties, and the limitations of in vitro ECM models. It highlights the role of ECM in tissue homeostasis, particularly in regulating cell behavior via mechanotransduction, focusing on force-sensitive sensors like integrins, Piezo1, TRPV4, and YAP/TAZ. Additionally, the review explores ECM remodeling in cancer, fibrosis, and cardiovascular diseases, along with current therapeutic strategies targeting ECM components, such as nanotechnology-based therapies, small molecule inhibitors, and CAF-targeted therapies. Challenges and clinical applications of these therapies are also discussed. Finally, the review looks ahead to future research, emphasizing the integration of ECM-targeted therapies in precision medicine and novel approaches to normalizing ECM composition and structure for therapeutic benefits. This review provides mechanobiological insights into therapeutic strategies targeting the ECM.
细胞外基质（ECM）是一个动态的三维网络，它提供结构支撑并调节关键的生物学过程，包括细胞黏附、迁移、分化和信号转导。其机械特性，如硬度、拓扑结构和粘弹性，在正常和病理条件下都至关重要，通过机械转导途径影响细胞行为。ECM的失调与多种疾病相关，因此全面了解其组成和特性至关重要。本综述讨论了ECM的组成、物理特性以及体外ECM模型的局限性。它强调了ECM在组织稳态中的作用，特别是通过机械转导调节细胞行为，重点关注整合素、Piezo1、TRPV4和YAP/TAZ等力敏传感器。此外，本综述探讨了癌症、纤维化和心血管疾病中的ECM重塑，以及目前针对ECM成分的治疗策略，如基于纳米技术的疗法、小分子抑制剂和针对癌症相关成纤维细胞（CAF）的疗法。还讨论了这些疗法的挑战和临床应用。最后，本综述展望了未来的研究，强调将针对ECM的疗法整合到精准医学中，以及采用新方法使ECM组成和结构正常化以获得治疗益处。本综述提供了针对ECM的治疗策略的机械生物学见解。
