Endothelial to Mesenchymal Transition (EndoMT) in the Pathogenesis of Human Fibrotic Diseases.
Endothelial to Mesenchymal Transition (EndoMT) in the Pathogenesis of Human Fibrotic Diseases.
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DOI：
10.3390/jcm5040045
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发表时间：
2016-04-11
影响因子：
3.9
通讯作者：
Jimenez SA
中科院分区：
文献类型：
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作者：
Piera-Velazquez S;Mendoza FA;Jimenez SA
纤维化疾病涵盖广泛的临床实体，包括系统性纤维化疾病，如系统性硬化症、硬皮病移植物抗宿主病、肾源性系统性纤维化和IgG 4相关硬化性疾病，以及许多器官特异性病症，包括辐射诱导的纤维化和心脏、肺、肝和肾纤维化。虽然它们的致病机制是相当不同的，这些疾病的共同特征是纤维组织大分子在受影响的器官中不受控制和进行性积累，导致其功能障碍和最终失败。纤维化疾病的发病机制是复杂的，尽管进行了广泛的研究，但仍然难以捉摸。许多研究已经确定肌成纤维细胞作为负责纤维化过程的建立和进展的细胞。纤维化疾病中的组织肌成纤维细胞来源于几种来源，包括静止的组织成纤维细胞、循环的CD34+纤维细胞和各种细胞类型（包括上皮细胞和内皮细胞）向活化的肌成纤维细胞的表型转化。然而，内皮细胞向间充质细胞的表型转化（内皮细胞向间充质细胞转化或EndoMT）在纤维化疾病的发病机制中的作用尚未完全阐明。在这里，我们审查的证据支持EndoMT的贡献，人类纤维化疾病的发病机制。
Fibrotic diseases encompass a wide spectrum of clinical entities including systemic fibrotic diseases such as systemic sclerosis, sclerodermatous graft versus host disease, nephrogenic systemic fibrosis, and IgG4-associated sclerosing disease, as well as numerous organ-specific disorders including radiation-induced fibrosis, and cardiac, pulmonary, liver, and kidney fibrosis. Although their causative mechanisms are quite diverse, these diseases share the common feature of an uncontrolled and progressive accumulation of fibrous tissue macromolecules in affected organs leading to their dysfunction and ultimate failure. The pathogenesis of fibrotic diseases is complex and despite extensive investigation has remained elusive. Numerous studies have identified myofibroblasts as the cells responsible for the establishment and progression of the fibrotic process. Tissue myofibroblasts in fibrotic diseases originate from several sources including quiescent tissue fibroblasts, circulating CD34+ fibrocytes, and the phenotypic conversion of various cell types including epithelial and endothelial cells into activated myofibroblasts. However, the role of the phenotypic transition of endothelial cells into mesenchymal cells (Endothelial to Mesenchymal Transition or EndoMT) in the pathogenesis of fibrotic disorders has not been fully elucidated. Here, we review the evidence supporting EndoMT’s contribution to human fibrotic disease pathogenesis.