Epithelial-to-mesenchymal and endothelial-to-mesenchymal transition: from cardiovascular development to disease.
Epithelial-to-mesenchymal and endothelial-to-mesenchymal transition: from cardiovascular development to disease.
复制标题
DOI：
10.1161/circulationaha.111.040352
复制
发表时间：
2012-04-10
期刊：
影响因子：
37.8
通讯作者：
Fuster V
中科院分区：
文献类型：
--
作者：
Kovacic JC;Mercader N;Torres M;Boehm M;Fuster V
细胞从上皮到间充质表型的转换，以及从间充质到上皮表型的转换，是哺乳动物生物从受孕到死亡的重要生物学过程。事实上，细胞在这些状态之间切换的能力一直是整个进化过程中产生复杂身体模式的基础。从上皮细胞到间充质细胞的表型转换，被称为上皮-间充质细胞转变(EMT)，是从对早期胚胎发育的大量观察中演变而来的范式，其基础可以追溯到20世纪20年代，以及Johannes Holtfreter在胚胎形成和分化方面的开创性工作。1、2到20世纪60年代末，伊丽莎白·海德对鸡种胚胎的研究导致了第一个正式的描述，即上皮细胞可以经历戏剧性的表型转化并产生胚胎中胚层。4随后的研究表明，这一过程是可逆的(间充质-上皮转化[MET])，逐渐地，术语“转化”取代了“转化”。鉴于EMT/MET最初是由发育生物学家识别和描述的，因此在胚胎植入和发育期间对这些过程进行最好的理解可能并不令人惊讶。在这篇综述中，现在已经知道，细胞从上皮细胞到间充质细胞再到上皮细胞状态的连续波是正常胚胎构型和器官形成所必需的。此外，大量跨越各种生理和病理条件的研究扩大了我们对EMT/MET的认识，现在为这些过程在各种成人条件下发挥的重要作用提供了证据，包括纤维化、伤口修复、炎症和恶性肿瘤。事实上，我们的概念框架现在还包括几种不同的细胞表型转换和子类别，包括内皮细胞到间充质细胞的转变(EndMT)。在这篇综述中，上皮细胞、内皮细胞和间充质细胞的表型转换将在心血管系统中进行探索，从心血管发育到成人终末器官疾病。将审查最新科学进展的关键领域，包括最新的发展和病理见解，这可能会导致新的治疗机会。
Cellular switching from an epithelial-to-mesenchymal phenotype, and conversely from a mesenchymal-toepithelial phenotype, are important biological programs that are operative from conception to death in mammalian organisms. Indeed, the capacity of cells to switch between these states has been fundamental to the generation of complex body patterns throughout evolution. Phenotypic switching from an epithelial to mesenchymal cell, termed epithelial-tomesenchymal transition (EMT), was a paradigm that evolved from numerous observations on early embryonic development, the foundations of which date back to the 1920s and the pioneering work of Johannes Holtfreter on embryo formation and differentiation. 1, 2 By the late 1960s, seminal chick embryo studies by Elizabeth Hay3 led to the first formal description that epithelial cells can undergo a dramatic phenotypic transformation and give rise to embryonic mesoderm. 4 Subsequent studies have revealed that this process is reversible (mesenchymal-to-epithelial transition [MET]), and gradually the term “transition” has come to replace “transformation.” Given that EMT/MET was initially identified and described by developmental biologists, it is perhaps not surprising that these processes are best understood during embryonic implantation and development. As explored in this review, it is now known that successive waves of cellular transition, from an epithelial to mesenchymal and then back to an epithelial state, are required for normal embryonic patterning and organ formation. In addition, numerous studies that span a broad spectrum of physiological and pathological conditions have expanded our knowledge of EMT/MET and now provide evidence for the important role played by these processes in various adult conditions including fibrosis, wound repair, inflammation, and malignancy. Indeed, our conceptual framework now also encompasses several variations and subcategories of cellular phenotypic switching, including endothelial-to-mesenchymal transition (EndMT). In this review, epithelial, endothelial, and mesenchymal phenotypic cellular switching will be explored in the cardiovascular system, spanning cardiovascular development through to adult end organ disease. Key areas of recent scientific progress will be examined, including recent developmental and pathological insights, which potentially may lead to novel therapeutic opportunities.