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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.
Pubmed: (View Article at PubMed) PMID:23270756
DOI: Full-text: DOI:10.1016/j.yexcr.2012.12.019

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.


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CRRD Object Information
CRRD ID: 13210526
Created: 2017-09-02
Species: All species
Last Modified: 2017-09-02
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.