Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Am J Pathol. 2011 Sep;179(3):1074-80. doi: 10.1016/j.ajpath.2011.06.001. Epub 2011 Jul 19.
The accumulation of a large number of myofibroblasts is responsible for exaggerated and uncontrolled production of extracellular matrix during the development and progression of pathological fibrosis. Myofibroblasts in fibrotic tissues are derived from at least three sources: expansion and activation of resident tissue fibroblasts, transition of epithelial cells into mesenchymal cells (epithelial-mesenchymal transition, EMT), and tissue migration of bone marrow-derived circulating fibrocytes. Recently, endothelial to mesenchymal transition (EndoMT), a newly recognized type of cellular transdifferentiation, has emerged as another possible source of tissue myofibroblasts. EndoMT is a complex biological process in which endothelial cells lose their specific markers and acquire a mesenchymal or myofibroblastic phenotype and express mesenchymal cell products such as α smooth muscle actin (α-SMA) and type I collagen. Similar to EMT, EndoMT can be induced by transforming growth factor (TGF-β). Recent studies using cell-lineage analysis have demonstrated that EndoMT may be an important mechanism in the pathogenesis of pulmonary, cardiac, and kidney fibrosis, and may represent a novel therapeutic target for fibrotic disorders.
大量肌成纤维细胞的积累是导致病理性纤维化发展和进展过程中细胞外基质过度和失控产生的原因。纤维化组织中的肌成纤维细胞至少有三个来源：固有组织成纤维细胞的扩增和激活、上皮细胞向间充质细胞的转化（上皮-间充质转化，EMT）以及骨髓来源的循环成纤维细胞的组织迁移。最近，内皮细胞向间充质细胞转化（EndoMT），一种新发现的细胞转分化类型，已成为组织肌成纤维细胞的另一个可能来源。EndoMT 是一个复杂的生物学过程，在此过程中内皮细胞失去其特定的标志物，并获得间充质或肌成纤维细胞表型，并表达间充质细胞产物，如α平滑肌肌动蛋白（α-SMA）和 I 型胶原。与 EMT 相似，转化生长因子（TGF-β）可诱导 EndoMT。最近使用细胞谱系分析的研究表明，EndoMT 可能是肺、心脏和肾脏纤维化发病机制中的一个重要机制，并可能代表纤维化疾病的一个新的治疗靶点。
