GDF15/MIC-1 Functions As a Protective and Antihypertrophic Factor Released From the Myocardium in Association With SMAD Protein Activation
Top Cited Papers
- 17 February 2006
- journal article
- research article
- Published by Wolters Kluwer Health in Circulation Research
- Vol. 98 (3) , 342-350
- https://doi.org/10.1161/01.res.0000202804.84885.d0
Abstract
Here we identified growth-differentiation factor 15 (GDF15) (also known as MIC-1), a secreted member of the transforming growth factor (TGF)-β superfamily, as a novel antihypertrophic regulatory factor in the heart. GDF15 is not expressed in the normal adult heart but is induced in response to conditions that promote hypertrophy and dilated cardiomyopathy. To elucidate the function of GDF15 in the heart, we generated transgenic mice with cardiac-specific overexpression. GDF15 transgenic mice were normal but were partially resistant to pressure overload-induced hypertrophy. Expression of GDF15 in neonatal cardiomyocyte cultures by adenoviral-mediated gene transfer antagonized agonist-induced hypertrophy in vitro. Transient expression of GDF15 outside the heart by intravenous adenoviral delivery, or by direct injection of recombinant GDF15 protein, attenuated ventricular dilation and heart failure in muscle lim protein gene–targeted mice through an endocrine effect. Conversely, examination of Gdf15 gene-tar...Keywords
This publication has 34 references indexed in Scilit:
- AFos Dissociates Cardiac Myocyte Hypertrophy and Expression of the Pathological Gene ProgramCirculation, 2005
- CARDIOPROTECTIVE FUNCTIONS OF ATRIAL NATRIURETIC PEPTIDE AND B‐TYPE NATRIURETIC PEPTIDE: A BRIEF REVIEWClinical and Experimental Pharmacology and Physiology, 2004
- Adaptive and maladaptive hypertrophic pathways: points of convergence and divergencePublished by Oxford University Press (OUP) ,2004
- Calcineurin/NFAT Coupling Participates in Pathological, but not Physiological, Cardiac HypertrophyCirculation Research, 2004
- Smad-dependent and Smad-independent pathways in TGF-β family signallingNature, 2003
- GATA- and Smad1-Dependent Enhancers in the Smad7 Gene Differentially Interpret Bone Morphogenetic Protein ConcentrationsMolecular and Cellular Biology, 2003
- Growth Differentiation Factor-15 Prevents Low Potassium-induced Cell Death of Cerebellar Granule Neurons by Differential Regulation of Akt and ERK PathwaysJournal of Biological Chemistry, 2003
- Stretch-activated pathways and left ventricular remodelingJournal of Cardiac Failure, 2002
- The Transcription Factor GATA4 Is Activated by Extracellular Signal-Regulated Kinase 1- and 2-Mediated Phosphorylation of Serine 105 in CardiomyocytesMolecular and Cellular Biology, 2001
- Expression of a TGF-β superfamily protein, macrophage inhibitory cytokine-1, in the yeast Pichia pastorisGene, 2000