Targeted Sprouty1 overexpression in cardiac myocytes does not alter myocardial remodeling or function.
The mitogen activated protein kinase (MAPK) signaling pathway regulates multiple events leading to heart failure including ventricular remodeling, contractility, hypertrophy, apoptosis, and fibrosis. The regulation of conserved intrinsic inhibitors of this pathway is poorly understood. We recently identified an up-regulation of Sprouty1 (Spry1) in a targeted approach for novel inhibitors of the MAPK signaling pathway in failing human hearts following reverse remodeling. The goal of this study was to test the hypothesis that up-regulated expression of Spry1 in cardiac myocytes would be sufficient to inhibit ERK1/2 activation and tissue remodeling. We established a murine model with up-regulated Spry1 expression in cardiac myocytes using the alpha-myosin heavy chain promoter (alpha-MHC). Heart weight and cardiac myocyte morphology were unchanged in adult male alpha-MHC-Spry1 mice compared to control mice. Ventricular function of alpha-MHC-Spry1 mice was unaltered at 8 weeks or 1 year of age. These findings were consistent with the lack of an effect of Spry1 on ERK1/2 activity. In summary, targeted up-regulation of Spry1 in cardiac myocytes is not sufficient to alter cell or tissue remodeling consistent with the lack of an effect on ERK1/2 activity.
Charles
Nathan J
NJ
Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
Huebert
Robert C
RC
Lee
Sangjin
S
Adhikari
Neeta
N
Polster
Sean
S
Rider
James E
JE
Braunlin
Elizabeth
E
Mariash
Ami
A
Robledo
Maggie
M
Schuweiler
David
D
Hall
Jennifer L
JL
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006321:Heart / Q000254:growth & development; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics; D010750:Phosphoproteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015854:Up-Regulation; D020257:Ventricular Remodeling / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C425468:Spry1 protein, mouse; D020928:Mitogen-Activated Protein Kinases; D018995:Myosin Heavy Chains
J Endocrinol. 2009 Nov;203(2):191-202
19423641
Nature. 2008 Dec 18;456(7224):980-4
19043405
Cardiology. 2003;100(1):17-22
12975541
Physiol Genomics. 2004 Aug 11;18(3):284-9
15306693
Am J Physiol. 1999 Nov;277(5):H1967-74
10564153
Cardiovasc Res. 2003 Aug 1;59(2):390-9
12909322
Circulation. 1998 Jun 16;97(23):2316-22
9639375
Nat Rev Mol Cell Biol. 2006 Aug;7(8):589-600
16936699
J Cell Sci. 2005 Dec 15;118(Pt 24):5861-71
16339969
Circ Res. 2000 Sep 29;87(7):574-80
11009562
Circ Res. 2001 Jan 19;88(1):88-96
11139479
Physiol Genomics. 2003 May 13;13(3):227-39
12746467
Cell. 1998 Jan 23;92(2):253-63
9458049
Nat Rev Mol Cell Biol. 2004 Jun;5(6):441-50
15173823
Nat Cell Biol. 2002 Nov;4(11):850-8
12402043
Circulation. 1998 Aug 18;98(7):656-62
9715858
Am J Physiol Heart Circ Physiol. 2007 Jan;292(1):H516-21
16936011
Dev Cell. 2005 Feb;8(2):229-39
15691764
Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2979-84
9501201
Cardiovasc Res. 2005 Dec 1;68(3):376-86
16024006