Tschumperlin Daniel J
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
Ann Am Thorac Soc. 2015 Mar;12 Suppl 1(Suppl 1):S24-9. doi: 10.1513/AnnalsATS.201407-320MG.
The extracellular matrix (ECM) of the lung serves as both a scaffold for resident cells and a mechanical support for respiratory function. The ECM is deposited during development and undergoes continuous turnover and maintenance during organ growth and homeostasis. Cells of the mesenchyme, including the tissue resident fibroblast, take a leading role in depositing and organizing the matrix and do so in an anatomically distinct fashion, with differing composition, organization, and mechanical properties within the airways, vessels, and alveoli of the lung. Recent technological advancements have allowed the lung's ECM biochemical composition and mechanical properties to be studied with improved resolution, thereby identifying novel disease-related changes in ECM characteristics. In parallel, efforts to study cells seeded on normal and disease-derived matrices have illustrated the powerful role the ECM can play in altering key functions of lung resident cells. The mechanical properties of the matrix have been identified as an important modifier of cell-matrix adhesions, with matrices of pathologic stiffness promoting profibrotic signaling and cell function. Ongoing work is identifying both mechanically activated pathways in mesenchymal cells and disease-related ECM molecules that biochemically regulate cell function. Uncovering the control systems by which cells respond to and regulate the matrix, and the failures in these systems that underlie aberrant repair, remains a major challenge. Progress in this area will be an essential element in efforts to engineer functional lung tissue for regenerative approaches and will be key to identifying new therapeutic strategies for lung diseases characterized by disturbed matrix architecture.
肺的细胞外基质（ECM）既是驻留细胞的支架，也是呼吸功能的机械支撑。ECM在发育过程中沉积，并在器官生长和稳态维持期间经历持续的更新和维护。间充质细胞，包括组织驻留成纤维细胞，在基质的沉积和组织过程中起主导作用，并且以解剖学上不同的方式进行，在肺的气道、血管和肺泡内具有不同的组成、组织和机械性能。最近的技术进步使得能够以更高的分辨率研究肺ECM的生化组成和机械性能，从而识别出与疾病相关的ECM特征的新变化。与此同时，对接种在正常和疾病来源基质上的细胞进行研究的努力表明，ECM在改变肺驻留细胞的关键功能方面可以发挥强大作用。基质的机械性能已被确定为细胞-基质粘附的重要调节因子，具有病理硬度的基质促进促纤维化信号传导和细胞功能。正在进行的工作正在识别间充质细胞中的机械激活途径以及生化调节细胞功能的与疾病相关的ECM分子。揭示细胞对基质作出反应并调节基质的控制系统，以及这些系统中导致异常修复的故障，仍然是一项重大挑战。这一领域的进展将是为再生方法设计功能性肺组织的努力中的一个基本要素，并且将是识别以基质结构紊乱为特征的肺部疾病新治疗策略的关键。
