miR-21 promotes fibrogenic epithelial-to-mesenchymal transition of epicardial mesothelial cells involving Programmed Cell Death 4 and Sprouty-1.

The lining of the adult heart contains epicardial mesothelial cells (EMCs) that have the potential to undergo fibrogenic Epithelial-to-Mesenchymal Transition (EMT) during cardiac injury. EMT of EMCs has therefore been suggested to contribute to the heterogeneous fibroblast pool that mediates cardiac...

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Main Authors: Hasse Brønnum, Ditte C Andersen, Mikael Schneider, Maria B Sandberg, Tilde Eskildsen, Solveig B Nielsen, Raghu Kalluri, Søren P Sheikh
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3575372?pdf=render
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author Hasse Brønnum
Ditte C Andersen
Mikael Schneider
Maria B Sandberg
Tilde Eskildsen
Solveig B Nielsen
Raghu Kalluri
Søren P Sheikh
author_facet Hasse Brønnum
Ditte C Andersen
Mikael Schneider
Maria B Sandberg
Tilde Eskildsen
Solveig B Nielsen
Raghu Kalluri
Søren P Sheikh
author_sort Hasse Brønnum
collection DOAJ
description The lining of the adult heart contains epicardial mesothelial cells (EMCs) that have the potential to undergo fibrogenic Epithelial-to-Mesenchymal Transition (EMT) during cardiac injury. EMT of EMCs has therefore been suggested to contribute to the heterogeneous fibroblast pool that mediates cardiac fibrosis. However, the molecular basis of this process is poorly understood. Recently, microRNAs (miRNAs) have been shown to regulate a number of sub-cellular events in cardiac disease. Hence, we hypothesized that miRNAs regulate fibrogenic EMT in the adult heart. Indeed pro-fibrogenic stimuli, especially TGF-β, promoted EMT progression in EMC cultures, which resulted in differential expression of numerous miRNAs, especially the pleiotropic miR-21. Accordingly, ectopic expression of miR-21 substantially promoted the fibroblast-like phenotype arising from fibrogenic EMT, whereas an antagonist that targeted miR-21 blocked this effect, as assessed on the E-cadherin/α-smooth muscle actin balance, cell viability, matrix activity, and cell motility, thus making miR-21 a relevant target of EMC-derived fibrosis. Several mRNA targets of miR-21 was differentially regulated during fibrogenic EMT of EMCs and miR-21-dependent targeting of Programmed Cell Death 4 (PDCD4) and Sprouty Homolog 1 (SPRY1) significantly contributed to the development of a fibroblastoid phenotype. However, PDCD4- and SPRY1-targeting was not entirely ascribable to all phenotypic effects from miR-21, underscoring the pleiotropic biological role of miR-21 and the increasing number of recognized miR-21 targets.
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spelling doaj.art-9d8bdbf6e7f8456fa74cc5fdb4733df32022-12-21T18:21:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5628010.1371/journal.pone.0056280miR-21 promotes fibrogenic epithelial-to-mesenchymal transition of epicardial mesothelial cells involving Programmed Cell Death 4 and Sprouty-1.Hasse BrønnumDitte C AndersenMikael SchneiderMaria B SandbergTilde EskildsenSolveig B NielsenRaghu KalluriSøren P SheikhThe lining of the adult heart contains epicardial mesothelial cells (EMCs) that have the potential to undergo fibrogenic Epithelial-to-Mesenchymal Transition (EMT) during cardiac injury. EMT of EMCs has therefore been suggested to contribute to the heterogeneous fibroblast pool that mediates cardiac fibrosis. However, the molecular basis of this process is poorly understood. Recently, microRNAs (miRNAs) have been shown to regulate a number of sub-cellular events in cardiac disease. Hence, we hypothesized that miRNAs regulate fibrogenic EMT in the adult heart. Indeed pro-fibrogenic stimuli, especially TGF-β, promoted EMT progression in EMC cultures, which resulted in differential expression of numerous miRNAs, especially the pleiotropic miR-21. Accordingly, ectopic expression of miR-21 substantially promoted the fibroblast-like phenotype arising from fibrogenic EMT, whereas an antagonist that targeted miR-21 blocked this effect, as assessed on the E-cadherin/α-smooth muscle actin balance, cell viability, matrix activity, and cell motility, thus making miR-21 a relevant target of EMC-derived fibrosis. Several mRNA targets of miR-21 was differentially regulated during fibrogenic EMT of EMCs and miR-21-dependent targeting of Programmed Cell Death 4 (PDCD4) and Sprouty Homolog 1 (SPRY1) significantly contributed to the development of a fibroblastoid phenotype. However, PDCD4- and SPRY1-targeting was not entirely ascribable to all phenotypic effects from miR-21, underscoring the pleiotropic biological role of miR-21 and the increasing number of recognized miR-21 targets.http://europepmc.org/articles/PMC3575372?pdf=render
spellingShingle Hasse Brønnum
Ditte C Andersen
Mikael Schneider
Maria B Sandberg
Tilde Eskildsen
Solveig B Nielsen
Raghu Kalluri
Søren P Sheikh
miR-21 promotes fibrogenic epithelial-to-mesenchymal transition of epicardial mesothelial cells involving Programmed Cell Death 4 and Sprouty-1.
PLoS ONE
title miR-21 promotes fibrogenic epithelial-to-mesenchymal transition of epicardial mesothelial cells involving Programmed Cell Death 4 and Sprouty-1.
title_full miR-21 promotes fibrogenic epithelial-to-mesenchymal transition of epicardial mesothelial cells involving Programmed Cell Death 4 and Sprouty-1.
title_fullStr miR-21 promotes fibrogenic epithelial-to-mesenchymal transition of epicardial mesothelial cells involving Programmed Cell Death 4 and Sprouty-1.
title_full_unstemmed miR-21 promotes fibrogenic epithelial-to-mesenchymal transition of epicardial mesothelial cells involving Programmed Cell Death 4 and Sprouty-1.
title_short miR-21 promotes fibrogenic epithelial-to-mesenchymal transition of epicardial mesothelial cells involving Programmed Cell Death 4 and Sprouty-1.
title_sort mir 21 promotes fibrogenic epithelial to mesenchymal transition of epicardial mesothelial cells involving programmed cell death 4 and sprouty 1
url http://europepmc.org/articles/PMC3575372?pdf=render
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