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miR-145 is differentially regulated by TGF-β(1) and ischaemia and targets Disabled-2 expression and wnt/β-catenin activity
The effect of wnt/β-catenin signalling in the response to acute myocardial infarction (AMI) remains controversial. The membrane receptor adaptor protein Disabled-2 (Dab2) is a tumour suppressor protein and has a critical role in stem cell specification. We recently demonstrated that down-regulation...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365889/ https://www.ncbi.nlm.nih.gov/pubmed/21762377 http://dx.doi.org/10.1111/j.1582-4934.2011.01385.x |
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author | Mayorga, Maritza E Penn, Marc S |
author_facet | Mayorga, Maritza E Penn, Marc S |
author_sort | Mayorga, Maritza E |
collection | PubMed |
description | The effect of wnt/β-catenin signalling in the response to acute myocardial infarction (AMI) remains controversial. The membrane receptor adaptor protein Disabled-2 (Dab2) is a tumour suppressor protein and has a critical role in stem cell specification. We recently demonstrated that down-regulation of Dab2 regulates cardiac protein expression and wnt/β-catenin activity in mesenchymal stem cells (MSC) in response to transforming growth factor-β(1) (TGF-β(1)). Although Dab2 expression has been shown to have effects in stem cells and tumour suppression, the molecular mechanisms regulating this expression are still undefined. We identified putative binding sites for miR-145 in the 3′-UTR of Dab2. In MSC in culture, we observed that TGF-β(1) treatment led to rapid and sustained up-regulation of pri–miR-145. Through gain and loss of function studies we demonstrate that miR-145 up-regulation was required for the down-regulation of Dab2 and increased β-catenin activity in response to TGF-β(1). To begin to define how Dab2 might regulate wnt/β-catenin in the heart following AMI, we quantified myocardial Dab2 as a function of time after left anterior descending ligation. There was no significant Dab2 expression in sham-operated myocardium. Following AMI, Dab2 levels were rapidly up-regulated in cardiac myocytes in the infarct border zone. The increase in cardiac myocyte Dab2 expression correlated with the rapid and sustained down-regulation of myocardial pri–miR-145 expression following AMI. Our data demonstrate a novel and critical role for miR-145 expression as a regulator of Dab2 expression and β-catenin activity in response to TGF-β(1) and hypoxia. |
format | Online Article Text |
id | pubmed-4365889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-43658892015-03-27 miR-145 is differentially regulated by TGF-β(1) and ischaemia and targets Disabled-2 expression and wnt/β-catenin activity Mayorga, Maritza E Penn, Marc S J Cell Mol Med Original Articles The effect of wnt/β-catenin signalling in the response to acute myocardial infarction (AMI) remains controversial. The membrane receptor adaptor protein Disabled-2 (Dab2) is a tumour suppressor protein and has a critical role in stem cell specification. We recently demonstrated that down-regulation of Dab2 regulates cardiac protein expression and wnt/β-catenin activity in mesenchymal stem cells (MSC) in response to transforming growth factor-β(1) (TGF-β(1)). Although Dab2 expression has been shown to have effects in stem cells and tumour suppression, the molecular mechanisms regulating this expression are still undefined. We identified putative binding sites for miR-145 in the 3′-UTR of Dab2. In MSC in culture, we observed that TGF-β(1) treatment led to rapid and sustained up-regulation of pri–miR-145. Through gain and loss of function studies we demonstrate that miR-145 up-regulation was required for the down-regulation of Dab2 and increased β-catenin activity in response to TGF-β(1). To begin to define how Dab2 might regulate wnt/β-catenin in the heart following AMI, we quantified myocardial Dab2 as a function of time after left anterior descending ligation. There was no significant Dab2 expression in sham-operated myocardium. Following AMI, Dab2 levels were rapidly up-regulated in cardiac myocytes in the infarct border zone. The increase in cardiac myocyte Dab2 expression correlated with the rapid and sustained down-regulation of myocardial pri–miR-145 expression following AMI. Our data demonstrate a novel and critical role for miR-145 expression as a regulator of Dab2 expression and β-catenin activity in response to TGF-β(1) and hypoxia. Blackwell Publishing Ltd 2012-05 2012-04-26 /pmc/articles/PMC4365889/ /pubmed/21762377 http://dx.doi.org/10.1111/j.1582-4934.2011.01385.x Text en Copyright © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. |
spellingShingle | Original Articles Mayorga, Maritza E Penn, Marc S miR-145 is differentially regulated by TGF-β(1) and ischaemia and targets Disabled-2 expression and wnt/β-catenin activity |
title | miR-145 is differentially regulated by TGF-β(1) and ischaemia and targets Disabled-2 expression and wnt/β-catenin activity |
title_full | miR-145 is differentially regulated by TGF-β(1) and ischaemia and targets Disabled-2 expression and wnt/β-catenin activity |
title_fullStr | miR-145 is differentially regulated by TGF-β(1) and ischaemia and targets Disabled-2 expression and wnt/β-catenin activity |
title_full_unstemmed | miR-145 is differentially regulated by TGF-β(1) and ischaemia and targets Disabled-2 expression and wnt/β-catenin activity |
title_short | miR-145 is differentially regulated by TGF-β(1) and ischaemia and targets Disabled-2 expression and wnt/β-catenin activity |
title_sort | mir-145 is differentially regulated by tgf-β(1) and ischaemia and targets disabled-2 expression and wnt/β-catenin activity |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365889/ https://www.ncbi.nlm.nih.gov/pubmed/21762377 http://dx.doi.org/10.1111/j.1582-4934.2011.01385.x |
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