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

Autor: Anne Yaël Nossent, Mikael Schneider, Hasse Brønnum, Solveig B. Nielsen, Ditte Caroline Andersen, Søren P. Sheikh
Rok vydání: 2012
Předmět:
Epithelial-Mesenchymal Transition
Myocardium/metabolism
Fibrosis/genetics
LIM-Homeodomain Proteins
Regulator
Transcription Factors/genetics
Gene Expression Regulation/drug effects
Epithelium/drug effects
Biology
RNA
Small Interfering/pharmacology
Epithelium
Epithelial Cells/drug effects
Rats
Sprague-Dawley
LIM-Homeodomain Proteins/genetics
microRNA
MicroRNAs/metabolism
Animals
Epithelial–mesenchymal transition
Progenitor cell
Islet-1
RNA
Small Interfering
Nuclear Proteins/antagonists & inhibitors
Cells
Cultured
Trans-Activators/antagonists & inhibitors
Myocardium
Mesenchymal stem cell
MicroRNA-31
Nuclear Proteins
Epithelial Cells
Cell Biology
Anatomy
Epicardium
Fibroblasts
Fibrosis
Cell biology
Rats
Fibroblasts/drug effects
Pericardium/cytology
MicroRNAs
Epithelial-to-mesenchymal transition
Gene Expression Regulation
embryonic structures
ISL1
Trans-Activators
Epithelial-Mesenchymal Transition/drug effects
Myofibroblast
Pericardium
Mesothelial Cell
Transcription Factors
Zdroj: Brønnum, H, Andersen, D C, Schneider, M, Yaël Nossent, A, Nielsen, S B & Sheikh, S P 2013, ' Islet-1 is a dual regulator of fibrogenic epithelial-to-mesenchymal transition in epicardial mesothelial cells ', Experimental Cell Research, vol. 319, no. 4, pp. 424-435 . https://doi.org/10.1016/j.yexcr.2012.12.019
ISSN: 1090-2422
Popis: 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-β-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 β-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 shows that Isl1 is a key regulatory molecule in adult cardiac EMT.
Databáze: OpenAIRE
Externí odkaz: