Role of the endothelial-to-mesenchymal transition in renal fibrosis of chronic kidney disease

• Published in: Clinical and experimental nephrology Vol. 17; no. 4; pp. 488 - 497
• Main Authors: He, Jianhua, Xu, Yong, Koya, Daisuke, Kanasaki, Keizo
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01-08-2013; Springer Nature B.V
• Subjects: Disease Progression; Endothelial Cells - metabolism; Endothelial Cells - pathology; Epithelial-Mesenchymal Transition; Fibrosis; Humans; Kidney - pathology; Kidney Diseases - pathology; Medicine; Medicine & Public Health; Myofibroblasts - metabolism; Nephrology; Renal Insufficiency, Chronic - pathology; Review Article; Transforming Growth Factor beta - physiology; Urology; Diabetes; EndMT; EMT; Transforming growth factor-β; MicroRNAs
• ISSN: 1342-1751; 1437-7799
• DOI: 10.1007/s10157-013-0781-0

All types of progressive chronic kidney disease (CKD) inevitably induce renal fibrosis, the hallmark of which is the activation and accumulation of a large number of matrix-producing fibroblasts or myofibroblasts. The activated fibroblasts or myofibroblasts are derived from diverse origins, such as residential fibroblasts, vascular pericytes, epithelial-to-mesenchymal transition (EMT), and bone marrow (circulating fibrocytes). Recently, endothelial-to-mesenchymal transition (EndMT) or endothelial-to-myofibroblast transition has also been suggested to promote fibrosis and is recognized as a novel mechanism for the generation of myofibroblasts. Similar to EMT, during EndMT, endothelial cells lose their adhesion and apical–basal polarity to form highly invasive, migratory, spindle-shaped, elongated mesenchymal cells. More importantly, biochemical changes accompany these distinct changes in cell polarity and morphology, including the decreased expression of endothelial markers and the acquisition of mesenchymal markers. This review highlights evidence supporting the important role of EndMT in the development of renal fibrosis in CKD and its underlying mechanisms, including novel biological significance of microRNA regulation.