miR-21 represses Pdcd4 during cardiac valvulogenesis
| Autor: | Russell A. Norris, Heather J. Kolpa, David S. Peal, Roger R. Markwald, Andrea C. Giokas, Calum A. MacRae, Joyce Bischoff, David J. Milan, Patrick T. Ellinor, Shibnath Ghatak, Stacey N. Lynch, Suniti Misra |
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| Rok vydání: | 2013 |
| Předmět: |
Time Factors
Endothelium Biology Mice Downregulation and upregulation Cell Movement microRNA medicine Animals Humans Molecular Biology Zebrafish Crosses Genetic Research Articles Regulation of gene expression Gene knockdown Atrioventricular valve Endothelial Cells Gene Expression Regulation Developmental RNA-Binding Proteins Zebrafish Proteins biology.organism_classification Heart Valves Molecular biology Cell biology Endothelial stem cell MicroRNAs medicine.anatomical_structure Apoptosis Regulatory Proteins Developmental Biology |
| Zdroj: | Development. 140:2172-2180 |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.084475 |
| Popis: | The discovery of small non-coding microRNAs has revealed novel mechanisms of post-translational regulation of gene expression, the implications of which are still incompletely understood. We focused on microRNA 21 (miR-21), which is expressed in cardiac valve endothelium during development, in order to better understand its mechanistic role in cardiac valve development. Using a combination of in vivo gene knockdown in zebrafish and in vitro assays in human cells, we show that miR-21 is necessary for proper development of the atrioventricular valve (AV). We identify pdcd4b as a relevant in vivo target of miR-21 and show that protection of pdcd4b from miR-21 binding results in failure of AV development. In vitro experiments using human pulmonic valve endothelial cells demonstrate that miR-21 overexpression augments endothelial cell migration. PDCD4 knockdown alone was sufficient to enhance endothelial cell migration. These results demonstrate that miR-21 plays a necessary role in cardiac valvulogenesis, in large part due to an obligatory downregulation of PDCD4. |
| Databáze: | OpenAIRE |
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