| Essential role for Smad3 in angiotensin II-induced tubular epithelial-mesenchymal transition. | |
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MedLine Citation:
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PMID: 20593491 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Angiotensin II (Ang II) is a key mediator of chronic kidney disease, in which epithelial-mesenchymal transition (EMT) is a critical process mediated by the TGFbeta/Smad signalling pathway. The present study examined the specific role of Smads in Ang II-induced EMT in vitro and in vivo. We found that Ang II signalled through the receptor of AT1, not AT2, to activate Smad2/3 and induce EMT in a normal rat tubular epithelial cell line (NRK52E). Activation of Smads by Ang II was attributed to degradation of an inhibitory Smad7, which was mediated by the AT1-Smurf2-dependent ubiquitin degradation mechanism because blockade of AT1 receptor or knockdown of Smurf2 inhibited Smad7 loss, thereby reducing Smad2/3 activation and EMT in response to Ang II. In contrast, over-expression of Smad7 inhibited Ang II-induced Smad2/3 activation and EMT in NRK52E cells and in a rat model of remnant kidney disease. Moreover, knockdown of Smad3, not Smad2, attenuated Ang II-induced EMT. In conclusion, Ang II activates Smad signalling to induce EMT, which is mediated by a loss of Smad7 through the AT1-Smurf2-dependent ubiquitin degradation pathway. Smad3, but not Smad2, may be a mediator of EMT, while Smad7 may play a protective role in EMT in response to Ang II. |
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Authors:
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Fuye Yang; Xiao Ru Huang; Arthur C K Chung; Chun-Cheng Hou; Kar Neng Lai; Hui Yao Lan |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of pathology Volume: 221 ISSN: 1096-9896 ISO Abbreviation: J. Pathol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-07 Completed Date: 2010-08-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0204634 Medline TA: J Pathol Country: England |
Other Details:
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Languages: eng Pagination: 390-401 Citation Subset: IM |
Affiliation:
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Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Shatin, NT, Hong Kong. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II
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pharmacology* Animals Cells, Cultured Dose-Response Relationship, Drug Epithelium / drug effects, pathology Gene Therapy / methods Kidney Diseases / metabolism, therapy Kidney Tubules / drug effects*, pathology, physiopathology Male Mesoderm / drug effects, pathology Rats Rats, Sprague-Dawley Receptor, Angiotensin, Type 1 / drug effects, physiology Receptor, Angiotensin, Type 2 / drug effects, physiology Signal Transduction / drug effects, physiology Smad Proteins, Receptor-Regulated / physiology Smad2 Protein / metabolism Smad3 Protein / physiology* Smad7 Protein / metabolism Ubiquitin / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Madh3 protein, rat; 0/Receptor, Angiotensin, Type 1; 0/Receptor, Angiotensin, Type 2; 0/Smad Proteins, Receptor-Regulated; 0/Smad2 Protein; 0/Smad3 Protein; 0/Smad7 Protein; 0/Ubiquitin; 11128-99-7/Angiotensin II |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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