Matrix, mesenchyme, and mechanotransduction.
Matrix, mesenchyme, and mechanotransduction.
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DOI：
10.1513/annalsats.201407-320mg
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发表时间：
2015-04
影响因子：
8.3
通讯作者：
D. Tschumperlin
中科院分区：
文献类型：
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作者：
D. Tschumperlin
肺的细胞外基质（ECM）既是驻留细胞的支架，又是呼吸功能的机械支持。ECM在发育过程中沉积，并在器官生长和体内平衡期间经历连续的周转和维持。间充质的细胞，包括组织驻留成纤维细胞，在沉积和组织基质中起主导作用，并且以解剖学上不同的方式这样做，在肺的气道、血管和肺泡内具有不同的组成、组织和机械性质。最近的技术进步已经允许以改进的分辨率研究肺的ECM生化组成和机械特性，从而识别ECM特征中的新的疾病相关变化。同时，研究接种在正常和疾病来源基质上的细胞的努力已经说明了ECM在改变肺驻留细胞的关键功能中可以发挥的强大作用。基质的机械性质已被确定为细胞-基质粘附的重要改性剂，具有病理硬度的基质促进促纤维化信号传导和细胞功能。正在进行的工作是确定间充质细胞中的机械激活途径和疾病相关的ECM分子，这些分子以生物化学方式调节细胞功能。揭示细胞响应和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，仍然是一个重大挑战。在这一领域的进展将是一个重要的因素，努力工程功能肺组织的再生方法，并将是关键，以确定新的治疗策略，肺部疾病的特点是紊乱的矩阵架构。
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.