Biology of fibroblasts and myofibroblasts.
Biology of fibroblasts and myofibroblasts.
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DOI：
10.1513/pats.200708-146dr
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发表时间：
2008-04-15
期刊：
影响因子：
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通讯作者：
Phan, Sem H
中科院分区：
文献类型：
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作者：
Phan, Sem H
尽管它们在纤维化中的重要性，但成纤维细胞的起源和以不同表型为特征的各种亚群的发生仍不清楚。各种研究已经描述了从经历重塑的肺组织中分离的成纤维细胞中的独特且相对稳定的表型，其不存在于正常完整组织中。这表明这些不同的成纤维细胞亚群可以从驻留的肺祖细胞或前体细胞从头产生和/或从远端器官如骨髓募集的过程。这些可能性的证据进行了审查，但目前还没有完全了解精确的前体细胞和各种表型之间的潜在相互关系，特别是它们如何与不同的肌成纤维细胞表型。此外，这些表型（如肌成纤维细胞）的发生机制的复杂性通过分化过程的多层次调节而突出，并有证据表明多种信号传导途径、转录因子和表观遗传机制的重要性。未来对这些不同的未解决领域的研究是必不可少的，以提供进一步的见解，可能有助于提供新的翻译方法的途径。
Despite their importance in fibrosis, the origin of fibroblasts and the genesis of the various subpopulations characterized by distinct phenotypes remain unclear. Various studies have described distinct and relatively stable phenotypes in fibroblasts isolated from lung tissue undergoing remodeling, which were not present in the normal intact tissue. This indicates a process by which these distinct fibroblast subpopulations could arise de novo from resident lung progenitors or precursor cells and/or be recruited from distal organs, such as the bone marrow. Evidence for these possibilities is reviewed, but there is as yet incomplete understanding of the precise precursor cells and the potential interrelationships between the various phenotypes, especially as to how they relate to the distinct myofibroblast phenotype. Moreover, the complexity of the mechanism for the genesis of these phenotypes, such as the myofibroblast, is highlighted by the multilevel regulation of the differentiation process, with evidence for the importance of multiple signaling pathways, transcription factors, and epigenetic mechanisms. Future studies into these various unsettled areas are essential to provide further insights that may help provide the pathway for novel translational approaches.