RGD Reference Report - Islet-1 is a dual regulator of fibrogenic epithelial-to-mesenchymal transition in epicardial mesothelial cells. - Rat Genome Database

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Islet-1 is a dual regulator of fibrogenic epithelial-to-mesenchymal transition in epicardial mesothelial cells.

Authors: Brønnum, Hasse  Andersen, Ditte C  Schneider, Mikael  Nossent, Anne Yaël  Nielsen, Solveig B  Sheikh, Søren P 
Citation: Brønnum H, etal., Exp Cell Res. 2013 Feb 15;319(4):424-35. doi: 10.1016/j.yexcr.2012.12.019. Epub 2012 Dec 24.
RGD ID: 13210526
Pubmed: PMID:23270756   (View Abstract at PubMed)
DOI: DOI:10.1016/j.yexcr.2012.12.019   (Journal Full-text)

Recent reports suggest that the adult epicardium is a source of cardiac progenitor cells having the ability to undergo epithelial-to-mesenchymal transition (EMT) and predominantly differentiate into myofibroblasts, thereby contributing to fibrosis of the stressed myocardium. Islet-1 (Isl1) is a widely applied marker of progenitor cells, including the epicardial mesothelial cells (EMCs). However, little is known of the general biological function of Islet-1, let alone its role in EMT of EMCs. Using rat-derived adult EMC cultures we therefore investigated the role of Isl1 expression in both non-stimulated EMCs and during TGF-ß-induced EMT. We found that Isl1 had a dual role by promoting mesenchymal features in non-stimulated EMCs, while a loss of Isl1 associated with EMT acted as a negative modulator of EMT progression as assessed on phenotype. We furthermore found that the loss of Isl1 expression during EMT was, in addition to transcriptional regulation by ß-catenin, mediated through direct targeting by microRNA-31 (miR-31). Through manipulations of miR-31 bioactivity in EMCs, we thus report that miR-31 is a negative modulator of cardiac fibrogenic EMT, primarily via targeting Isl1. Our data show that Isl1 is a key regulatory molecule in adult cardiac EMT.



Gene Ontology Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Ctnnb1  (catenin beta 1)
Isl1  (ISL LIM homeobox 1)
Mir31  (microRNA 31)
Myocd  (myocardin)


Additional Information