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https://hdl.handle.net/2440/61877
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dc.contributor.author | Wang, B. | - |
dc.contributor.author | Herman-Edelstein, M. | - |
dc.contributor.author | Koh, P. | - |
dc.contributor.author | Burns, W. | - |
dc.contributor.author | Jandeleit-Dahm, K. | - |
dc.contributor.author | Watson, A. | - |
dc.contributor.author | Saleem, M. | - |
dc.contributor.author | Goodall, G. | - |
dc.contributor.author | Twigg, S. | - |
dc.contributor.author | Cooper, M. | - |
dc.contributor.author | Kantharidis, P. | - |
dc.date.issued | 2010 | - |
dc.identifier.citation | Diabetes, 2010; 59(7):1794-1802 | - |
dc.identifier.issn | 0012-1797 | - |
dc.identifier.issn | 1939-327X | - |
dc.identifier.uri | http://hdl.handle.net/2440/61877 | - |
dc.description.abstract | OBJECTIVE--Increased deposition of extracellular matrix (ECM) within the kidney is driven by profibrotic mediators including transforming growth factor-[beta] (TGF-[beta]) and connective tissue growth factor (CTGF). We investigated whether some of their effects may be mediated through changes in expression of certain microRNAs (miRNAs). RESEARCH DESIGN AND METHODS--Proximal tubular cells, primary rat mesangial cells, and human podocytes were analyzed for changes in the expression of key genes, ECM proteins, and miRNA after exposure to TGF-[beta] (1-10 ng/[micro]l). Tubular cells were also infected with CTGF-adenovirus. Kidneys from diabetic apoE mice were also analyzed for changes in gene expression and miRNA levels. RESULTS--TGF-[beta] treatment was associated with morphologic and phenotypic changes typical of epithelial-mesenchymal transition (EMT) including increased fibrogenesis in all renal cell types and decreased E-cadherin expression in tubular cells. TGF-[beta] treatment also modulated the expression of certain miRNAs, including decreased expression of miR-192/215 in tubular cells, mesangial cells, which are also decreased in diabetic kidney. Ectopic expression of miR-192/215 increased E-cadherin levels via repressed translation of ZEB2 mRNA, in the presence and absence of TGF-[beta], as demonstrated by a ZEB2 3'-untranslated region luciferase reporter assay. However, ectopic expression of miR-192/215 did not affect the expression of matrix proteins or their induction by TGF-[beta]. In contrast, CTGF increased miR-192/215 levels, causing a decrease in ZEB2, and consequently increased E-cadherin mRNA. CONCLUSIONS--These data demonstrate the linking role of miRNA-192/215 and ZEB2 in TGF-[beta]/CTGF-mediated changes in E-cadherin expression. These changes appear to occur independently of augmentation of matrix protein synthesis, suggesting that a multistep EMT program is not necessary for fibrogenesis to occur. | - |
dc.description.statementofresponsibility | Bo Wang, Michal Herman-Edelstein, Philip Koh, Wendy Burns, Karin Jandeleit-Dahm, Anna Watson, Moin Saleem, Gregory J. Goodall, Stephen M. Twigg, Mark E. Cooper and Phillip Kantharidis | - |
dc.language.iso | en | - |
dc.publisher | Amer Diabetes Assoc | - |
dc.rights | © 2010 American Diabetes Association | - |
dc.source.uri | http://dx.doi.org/10.2337/db09-1736 | - |
dc.subject | Kidney | - |
dc.subject | Cells, Cultured | - |
dc.subject | Cell Line | - |
dc.subject | Epithelial Cells | - |
dc.subject | Animals | - |
dc.subject | Humans | - |
dc.subject | Mice | - |
dc.subject | Rats | - |
dc.subject | Fibrosis | - |
dc.subject | Transforming Growth Factor beta | - |
dc.subject | Cadherins | - |
dc.subject | MicroRNAs | - |
dc.subject | Blotting, Western | - |
dc.subject | Immunohistochemistry | - |
dc.subject | Reverse Transcriptase Polymerase Chain Reaction | - |
dc.subject | Cell Shape | - |
dc.subject | Gene Expression | - |
dc.title | E-cadherin expression is regulated by miR-192/215 by a mechanism that is independent of the profibrotic effects of transforming growth factor-β | - |
dc.title.alternative | E-cadherin expression is regulated by miR-192/215 by a mechanism that is independent of the profibrotic effects of transforming growth factor-beta | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.2337/db09-1736 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Goodall, G. [0000-0003-1294-0692] | - |
Appears in Collections: | Aurora harvest 5 Medicine publications |
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