White Eric S
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
Ann Am Thorac Soc. 2015 Mar;12 Suppl 1(Suppl 1):S30-3. doi: 10.1513/AnnalsATS.201406-240MG.
Extracellular matrix (ECM) is a tissue-specific macromolecular structure that provides physical support to tissues and is essential for normal organ function. In the lung, ECM plays an active role in shaping cell behavior both in health and disease by virtue of the contextual clues it imparts to cells. Qualities including dimensionality, molecular composition, and intrinsic stiffness all promote normal function of the lung ECM. Alterations in composition and/or modulation of stiffness of the focally injured or diseased lung ECM microenvironment plays a part in reparative processes performed by fibroblasts. Under conditions of remodeling or in disease states, inhomogeneous stiffening (or softening) of the pathologic ECM may both precede modifications in cell behavior and be a result of disease progression. The ability of ECM to stimulate further ECM production by fibroblasts and drive disease progression has potentially significant implications for mesenchymal stromal cell-based therapies; in the setting of pathologic ECM stiffness or composition, the therapeutic intent of progenitor cells may be subverted. Taken together, current data suggest that lung ECM actively contributes to health and disease; thus, mediators of cell-ECM signaling or factors that influence ECM stiffness may represent viable therapeutic targets in many lung disorders.
细胞外基质（ECM）是一种组织特异性大分子结构，为组织提供物理支撑，对正常器官功能至关重要。在肺中，ECM凭借其赋予细胞的背景线索，在健康和疾病状态下对细胞行为的塑造均发挥着积极作用。包括维度、分子组成和固有硬度在内的特性均有助于肺ECM的正常功能。局灶性损伤或患病肺ECM微环境的组成改变和/或硬度调节在成纤维细胞进行的修复过程中发挥作用。在重塑条件下或疾病状态下，病理性ECM的不均匀硬化（或软化）可能既先于细胞行为的改变，又是疾病进展的结果。ECM刺激成纤维细胞进一步产生ECM并推动疾病进展的能力，对基于间充质基质细胞的治疗具有潜在的重大意义；在病理性ECM硬度或组成的情况下，祖细胞的治疗意图可能会被颠覆。综上所述，目前的数据表明肺ECM在健康和疾病中均发挥着积极作用；因此，细胞-ECM信号传导介质或影响ECM硬度的因素可能是许多肺部疾病中可行的治疗靶点。
