title: Comparative transcriptome profiling of the injured zebrafish and mouse hearts identifies miRNA-dependent repair pathways.
abstract: OBJECTIVE
  The adult mammalian heart has poor regenerative capacity. In contrast, the zebrafish heart retains a robust capacity for regeneration into adulthood. These distinct responses are consequences of a differential utilization of evolutionary-conserved gene regulatory networks in the damaged heart. To systematically identify miRNA-dependent networks controlling cardiac repair following injury, we performed comparative gene and miRNA profiling of the cardiac transcriptome in adult mice and zebrafish.
  
  
  RESULTS
  Using an integrated approach, we show that 45 miRNA-dependent networks, involved in critical biological pathways, are differentially modulated in the injured zebrafish vs. mouse hearts. We study, more particularly, the miR-26a-dependent response. Therefore, miR-26a is down-regulated in the fish heart after injury, whereas its expression remains constant in the mouse heart. Targets of miR-26a involve activators of the cell cycle and Ezh2, a component of the polycomb repressive complex 2 (PRC2). Importantly, PRC2 exerts repressive functions on negative regulators of the cell cycle. In cultured neonatal cardiomyocytes, inhibition of miR-26a stimulates, therefore, cardiomyocyte proliferation. Accordingly, miR-26a knockdown prolongs the proliferative window of cardiomyocytes in the post-natal mouse heart.
  
  
  CONCLUSIONS
  This novel strategy identifies a series of miRNAs and associated pathways, in particular miR-26a, which represent attractive therapeutic targets for inducing repair in the injured heart.
authors: Experimental Cardiology Unit, Department of Medicine, University of Lausanne Medical School, Lausanne 1011, Switzerland.
authors: Stefania
authors: S
authors: Crippa
authors: Experimental Cardiology Unit, Department of Medicine, University of Lausanne Medical School, Lausanne 1011, Switzerland.
authors: Mohamed
authors: M
authors: Nemir
authors: Experimental Cardiology Unit, Department of Medicine, University of Lausanne Medical School, Lausanne 1011, Switzerland.
authors: Samir
authors: S
authors: Ounzain
authors: Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors: Mark
authors: M
authors: Ibberson
authors: Cardiovascular Assessment Facility, University of Lausanne, Lausanne, Switzerland.
authors: Corinne
authors: C
authors: Berthonneche
authors: Cardiovascular Assessment Facility, University of Lausanne, Lausanne, Switzerland.
authors: Alexandre
authors: A
authors: Sarre
authors: Institute for Research in Ophthalmology, Sion, Switzerland.
authors: Gaëlle
authors: G
authors: Boisset
authors: Experimental Cardiology Unit, Department of Medicine, University of Lausanne Medical School, Lausanne 1011, Switzerland.
authors: Damien
authors: D
authors: Maison
authors: Lausanne Genomic Technologies Facility, University of Lausanne, Lausanne, Switzerland.
authors: Keith
authors: K
authors: Harshman
authors: Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors: Ioannis
authors: I
authors: Xenarios
authors: Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland.
authors: Dario
authors: D
authors: Diviani
authors: Institute for Research in Ophthalmology, Sion, Switzerland.
authors: Daniel
authors: D
authors: Schorderet
authors: Experimental Cardiology Unit, Department of Medicine, University of Lausanne Medical School, Lausanne 1011, Switzerland thierry.pedrazzini@chuv.ch.
authors: Thierry
authors: T
authors: Pedrazzini
mesh_terms: D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks / Q000235:genetics*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000502:physiology; D012038:Regeneration; D014945:Wound Healing / Q000235:genetics*; D015027:Zebrafish
chemical_list: D035683:MicroRNAs
keywords: Mouse; Myocardial infarction; Repair mechanisms; Zebrafish; miRNAs