Distinct functions of junD in cardiac hypertrophy and heart failure.
Cardiac hypertrophic stimuli induce both adaptive and maladaptive growth response pathways in heart. Here we show that mice lacking junD develop less adaptive hypertrophy in heart after mechanical pressure overload, while cardiomyocyte-specific expression of junD in mice results in spontaneous ventricular dilation and decreased contractility. In contrast, fra-1 conditional knock-out mice have a normal hypertrophic response, whereas hearts from fra-1 transgenic mice decompensate prematurely. Moreover, fra-1 transgenic mice simultaneously lacking junD reveal a spontaneous dilated cardiomyopathy associated with increased cardiomyocyte apoptosis and a primary mitochondrial defect. These data suggest that junD promotes both adaptive-protective and maladaptive hypertrophy in heart, depending on its expression levels.
Ricci
Romeo
R
Institute of Molecular Pathology, A-1030 Vienna, Austria.
Eriksson
Urs
U
Oudit
Gavin Y
GY
Eferl
Robert
R
Akhmedov
Alexander
A
Sumara
Izabela
I
Sumara
Grzegorz
G
Kassiri
Zamaneh
Z
David
Jean-Pierre
JP
Bakiri
Latifa
L
Sasse
Bernd
B
Idarraga
Maria-Helena
MH
Rath
Martina
M
Kurz
David
D
Theussl
Hans-Christian
HC
Perriard
Jean-Claude
JC
Backx
Peter
P
Penninger
Josef M
JM
Wagner
Erwin F
EF
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D000099169:Fos-Related Antigen 1
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D000099169:Fos-Related Antigen 1