Journal ArticleDOI
Endothelial-to-mesenchymal transition contributes to cardiac fibrosis
Elisabeth M. Zeisberg,Oleg Tarnavski,Michael Zeisberg,Adam L. Dorfman,Julie R. McMullen,Erika Gustafsson,Anil Chandraker,Xueli Yuan,William T. Pu,Anita B. Roberts,Eric G. Neilson,Mohamed H. Sayegh,Seigo Izumo,Raghu Kalluri +13 more
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TLDR
It is shown that cardiac fibrosis is associated with the emergence of fibroblasts originating from endothelial cells, suggesting an endothelial-mesenchymal transition (EndMT) similar to events that occur during formation of the atrioventricular cushion in the embryonic heart.Abstract:
Cardiac fibrosis, associated with a decreased extent of microvasculature and with disruption of normal myocardial structures, results from excessive deposition of extracellular matrix, which is mediated by the recruitment of fibroblasts. The source of these fibroblasts is unclear and specific anti-fibrotic therapies are not currently available. Here we show that cardiac fibrosis is associated with the emergence of fibroblasts originating from endothelial cells, suggesting an endothelial-mesenchymal transition (EndMT) similar to events that occur during formation of the atrioventricular cushion in the embryonic heart. Transforming growth factor-β1 (TGF-β1) induced endothelial cells to undergo EndMT, whereas bone morphogenic protein 7 (BMP-7) preserved the endothelial phenotype. The systemic administration of recombinant human BMP-7 (rhBMP-7) significantly inhibited EndMT and the progression of cardiac fibrosis in mouse models of pressure overload and chronic allograft rejection. Our findings show that EndMT contributes to the progression of cardiac fibrosis and that rhBMP-7 can be used to inhibit EndMT and to intervene in the progression of chronic heart disease associated with fibrosis.read more
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Journal ArticleDOI
Epithelial-Mesenchymal Transitions in Development and Disease
Jean Paul Thiery,Jean Paul Thiery,Hervé Acloque,Ruby Yun-Ju Huang,Ruby Yun-Ju Huang,M. Angela Nieto +5 more
TL;DR: The mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.
Journal ArticleDOI
The basics of epithelial-mesenchymal transition
Raghu Kalluri,Robert A. Weinberg +1 more
TL;DR: Processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias and the identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes.
Journal ArticleDOI
Molecular mechanisms of epithelial–mesenchymal transition
TL;DR: The reprogramming of gene expression during EMT, as well as non-transcriptional changes, are initiated and controlled by signalling pathways that respond to extracellular cues, and the convergence of signalling pathways is essential for EMT.
Journal ArticleDOI
Cellular and molecular mechanisms of fibrosis.
TL;DR: Current understanding of the cellular and molecular mechanisms of fibrogenesis is explored and components of the renin–angiotensin–aldosterone system (ANG II) have been identified as important regulators of fibrosis and are being investigated as potential targets of antifibrotic drugs.
Journal ArticleDOI
TGF-beta-induced epithelial to mesenchymal transition.
TL;DR: The induction of EMT in response to TGF-β is discussed, and the underlying signaling and transcription mechanisms are focused on.
References
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Masayuki Iwano,David Plieth,Theodore M. Danoff,Theodore M. Danoff,Chengsen Xue,Hirokazu Okada,Hirokazu Okada,Eric G. Neilson +7 more
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BMP-7 counteracts TGF-β1–induced epithelial-to-mesenchymal transition and reverses chronic renal injury
Michael Zeisberg,Jun-ichi Hanai,Hikaru Sugimoto,Tadanori Mammoto,David M. Charytan,Frank Strutz,Raghu Kalluri +6 more
TL;DR: It is reported that BMP-7 reverses TGF-β1–induced epithelial-to-mesenchymal transition (EMT) by reinduction of E-cadherin, a key epithelial cell adhesion molecule, which provides evidence of cross talk between B MP-7 and TGF -β1 in the regulation of EMT in health and disease.
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Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response.
Gillian S. Ashcroft,Xiao Yang,Adam B. Glick,Michael Weinstein,John J. Letterio,Diane Mizel,Mario A. Anzano,Teresa Greenwell-Wild,Sharon M. Wahl,Chu-Xia Deng,Anita B. Roberts +10 more
TL;DR: It is reported that Smad3-null (Smad3ex8/ex8) mice paradoxically show accelerated cutaneous wound healing compared with wild-type mice, characterized by an increased rate of re-epithelialization and significantly reduced local infiltration of monocytes.