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

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Abstract

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.

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Acknowledgments

JH was supported by a foreign scholar grant from Kanazawa Medical University. YX is supported by the grant from National Natural Science Foundation of China (30670980), Education Bureau of Sichuan Province (10ZA036), and Ministry of human resources and social security of China (2009-26-366). KK is supported by grants from the Japan Society for the Promotion of Science (23790381). KK is currently also supported by several foundation grants, including the following: Japan Research Foundation for Clinical Pharmacology, Daiichi-Sankyo Foundation of Life Science, Ono Medical Research Foundation, The NOVARTIS Foundation (Japan) for the Promotion of Science, Banyu Foundation and the Takeda Science Foundation. Authors were supported by a Grant for Collaborative Research to DK (C2011-4, C2012-1) and a Grant for Promoted Research to KK (S2011-1, S2012-5) from Kanazawa Medical University.

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The authors declare that they have no competing interests.

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Correspondence to Keizo Kanasaki.

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He, J., Xu, Y., Koya, D. et al. Role of the endothelial-to-mesenchymal transition in renal fibrosis of chronic kidney disease. Clin Exp Nephrol 17, 488–497 (2013). https://doi.org/10.1007/s10157-013-0781-0

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