Xiao Lin, Dudley Andrew C
Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Department of Microbiology, Immunology, and Cancer Biology, The University of Virginia, Charlottesville, VA, 22908, USA.
J Pathol. 2017 Jan;241(1):25-35. doi: 10.1002/path.4814. Epub 2016 Nov 10.
In the heart and other organs, endothelial-mesenchymal transition (EndMT) has emerged as an important developmental process that involves coordinated migration, differentiation, and proliferation of the endothelium. In multiple disease states including cancer angiogenesis and cardiovascular disease, the processes that regulate EndMT are recapitulated, albeit in an uncoordinated and dysregulated manner. Members of the transforming growth factor beta (TGFβ) superfamily are well known to impart cellular plasticity during EndMT by the timely activation (or repression) of transcription factors and miRNAs in addition to epigenetic regulation of gene expression. On the other hand, fibroblast growth factors (FGFs) are reported to augment or oppose TGFβ-driven EndMT in specific contexts. Here, we have synthesized the currently understood roles of TGFβ and FGF signalling during EndMT and have provided a new, comprehensive paradigm that delineates how an autocrine and paracrine TGFβ/FGF axis coordinates endothelial cell specification and plasticity. We also provide new guidelines and nomenclature that considers factors such as endothelial cell heterogeneity to better define EndMT across different vascular beds. This perspective should therefore help to clarify why TGFβ and FGF can both cooperate with or oppose one another during the complex process of EndMT in both health and disease. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
在内脏及其他器官中，内皮-间充质转化（EndMT）已成为一个重要的发育过程，该过程涉及内皮细胞的协同迁移、分化和增殖。在包括癌症血管生成和心血管疾病在内的多种疾病状态下，尽管调控EndMT的过程是不协调且失调的，但这些过程仍会重现。众所周知，转化生长因子β（TGFβ）超家族的成员除了对基因表达进行表观遗传调控外，还通过及时激活（或抑制）转录因子和微小RNA（miRNA），在EndMT过程中赋予细胞可塑性。另一方面，据报道，成纤维细胞生长因子（FGF）在特定情况下会增强或拮抗TGFβ驱动的EndMT。在此，我们总结了目前所了解的TGFβ和FGF信号在EndMT过程中的作用，并提供了一个新的、全面的范例，阐述了自分泌和旁分泌TGFβ/FGF轴如何协调内皮细胞的特化和可塑性。我们还提供了新的指导方针和命名法，其中考虑了内皮细胞异质性等因素，以便更好地定义不同血管床中的EndMT。因此，这一观点应有助于阐明为什么在健康和疾病状态下，TGFβ和FGF在EndMT的复杂过程中既能相互协作，也能相互拮抗。版权所有© 2016英国及爱尔兰病理学会。由约翰·威利父子有限公司出版。
