(Circulation. 2001;103:2731.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Cardiac-Specific LIM Protein FHL2 Modifies the Hypertrophic Response to ß-Adrenergic Stimulation
From the Departments of Internal Medicine, Molecular Biology, and Pathology (J.A.R.), University of Texas Southwestern Medical Center, Dallas, Tex.
Correspondence to R. Sanders Williams, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, NB11.200, Dallas, TX 75390-8573. E-mail williams{at}ryburn.swmed.edu
Background—A deficiency of muscle LIM protein results in dilated cardiomyopathy, but the function of other LIM proteins in the heart has not been assessed previously. We have characterized the expression and function of FHL2, a heart-specific member of the LIM domain gene family.
Methods and Results—Expression of FHL2 mRNA and protein was examined by Northern blot, in situ hybridization, and Western blot analyses of fetal and adult mice. FHL2 transcripts are present at embryonic day (E) 7.5 within the cardiac crescent in a pattern that resembles that of Nkx2.5 mRNA. During later stages of cardiac development and in adult animals, FHL2 expression is localized to the myocardium and absent from endocardium, cardiac cushion, outflow tract, or coronary vasculature. The gene encoding FHL2 was disrupted by homologous recombination, and knockout mice devoid of FHL2 were found to undergo normal cardiovascular development. In the absence of FHL2, however, cardiac hypertrophy resulting from chronic infusion of isoproterenol is exaggerated (59% versus 20% increase in heart weight/body weight in FHL null versus wild-type mice; P<0.01).
Conclusions—FHL2 is an early marker of cardiogenic cells and a cardiac-specific LIM protein in the adult. FHL2 is not required for normal cardiac development but modifies the hypertrophic response to ß-adrenergic stimulation.
Key Words: hypertrophy • genetics • molecular biology • myocardium
This article has been cited by other articles:
 |
|
 |
|
  J. Park, C. Will, B. Martin, L. Gullotti, N. Friedrichs, R. Buettner, H. Schneider, S. Ludwig, and V. Wixler Deficiency in the LIM-only protein FHL2 impairs assembly of extracellular matrix proteins FASEB J, July 1, 2008; 22(7): 2508 - 2520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Labalette, Y. Nouet, J. Sobczak-Thepot, C. Armengol, F. Levillayer, M.-C. Gendron, C.-A. Renard, B. Regnault, J. Chen, M.-A. Buendia, et al. The LIM-only Protein FHL2 Regulates Cyclin D1 Expression and Cell Proliferation J. Biol. Chem., May 30, 2008; 283(22): 15201 - 15208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. W. Donker, J. G. Maessen, F. Verheyen, F. C. Ramaekers, R. L. H. M. G. Spatjens, H. Kuijpers, C. Ramakers, P. M. H. Schiffers, M. A. Vos, H. J. G. M. Crijns, et al. Impact of acute and enduring volume overload on mechanotransduction and cytoskeletal integrity of canine left ventricular myocardium Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2324 - H2332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Cottle, M. J. McGrath, B. S. Cowling, I. D. Coghill, S. Brown, and C. A. Mitchell FHL3 binds MyoD and negatively regulates myotube formation J. Cell Sci., April 15, 2007; 120(8): 1423 - 1435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Wixler, S. Hirner, J. M. Muller, L. Gullotti, C. Will, J. Kirfel, T. Gunther, H. Schneider, A. Bosserhoff, H. Schorle, et al. Deficiency in the LIM-only protein Fhl2 impairs skin wound healing J. Cell Biol., April 9, 2007; 177(1): 163 - 172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Peng, K. Raddatz, J. D. Molkentin, Y. Wu, S. Labeit, H. Granzier, and M. Gotthardt Cardiac Hypertrophy and Reduced Contractility in Hearts Deficient in the Titin Kinase Region Circulation, February 13, 2007; 115(6): 743 - 751. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sun, G. Yan, A. Ren, B. You, and J. K. Liao FHL2/SLIM3 Decreases Cardiomyocyte Survival by Inhibitory Interaction With Sphingosine Kinase-1 Circ. Res., September 1, 2006; 99(5): 468 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hoshijima Mechanical stress-strain sensors embedded in cardiac cytoskeleton: Z disk, titin, and associated structures Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1313 - H1325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Labalette, C.-A. Renard, C. Neuveut, M.-A. Buendia, and Y. Wei Interaction and Functional Cooperation between the LIM Protein FHL2, CBP/p300, and {beta}-Catenin Mol. Cell. Biol., December 15, 2004; 24(24): 10689 - 10702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Hill and P. R. Riley Differential Regulation of Hand1 Homodimer and Hand1-E12 Heterodimer Activity by the Cofactor FHL2 Mol. Cell. Biol., November 15, 2004; 24(22): 9835 - 9847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Samson, N. Smyth, S. Janetzky, O. Wendler, J. M. Muller, R. Schule, H. von der Mark, K. von der Mark, and V. Wixler The LIM-only Proteins FHL2 and FHL3 Interact with {alpha}- and {beta}-Subunits of the Muscle {alpha}7{beta}1 Integrin Receptor J. Biol. Chem., July 2, 2004; 279(27): 28641 - 28652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. H. Purcell, D. Darwis, O. F. Bueno, J. M. Muller, R. Schule, and J. D. Molkentin Extracellular Signal-Regulated Kinase 2 Interacts with and Is Negatively Regulated by the LIM-Only Protein FHL2 in Cardiomyocytes Mol. Cell. Biol., February 1, 2004; 24(3): 1081 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-L. Hsu, Y.-L. Chen, S. Yeh, H.-J. Ting, Y.-C. Hu, H. Lin, X. Wang, and C. Chang The Use of Phage Display Technique for the Isolation of Androgen Receptor Interacting Peptides with (F/W)XXL(F/W) and FXXLY New Signature Motifs J. Biol. Chem., June 20, 2003; 278(26): 23691 - 23698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. D. Coghill, S. Brown, D. L. Cottle, M. J. McGrath, P. A. Robinson, H. H. Nandurkar, J. M. Dyson, and C. A. Mitchell FHL3 Is an Actin-binding Protein That Regulates {alpha}-Actinin-mediated Actin Bundling: FHL3 LOCALIZES TO ACTIN STRESS FIBERS AND ENHANCES CELL SPREADING AND STRESS FIBER DISASSEMBLY J. Biol. Chem., June 20, 2003; 278(26): 24139 - 24152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lange, D. Auerbach, P. McLoughlin, E. Perriard, B. W. Schafer, J.-C. Perriard, and E. Ehler Subcellular targeting of metabolic enzymes to titin in heart muscle may be mediated by DRAL/FHL-2 J. Cell Sci., March 14, 2003; 115(24): 4925 - 4936. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Robinson, S. Brown, M. J. McGrath, I. D. Coghill, R. Gurung, and C. A. Mitchell Skeletal muscle LIM protein 1 regulates integrin-mediated myoblast adhesion, spreading, and migration Am J Physiol Cell Physiol, March 1, 2003; 284(3): C681 - C695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Schafer, P. Neuhaus, J. Kruse, and T. Braun The Homeobox Gene Lbx1 Specifies a Subpopulation of Cardiac Neural Crest Necessary for Normal Heart Development Circ. Res., January 10, 2003; 92(1): 73 - 80. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Knoll, M. Hoshijima, and K.R. Chien Z-line proteins: implications for additional functions Eur. Heart J. Suppl., December 1, 2002; 4(suppl_I): I13 - I17. [Abstract] [PDF]
|
|
|
|
|
|
B. Martin, R. Schneider, S. Janetzky, Z. Waibler, P. Pandur, M. Kuhl, J. Behrens, K. von der Mark, A. Starzinski-Powitz, and V. Wixler The LIM-only protein FHL2 interacts with {beta}-catenin and promotes differentiation of mouse myoblasts J. Cell Biol., October 14, 2002; 159(1): 113 - 122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kupershmidt, I. C.-H. Yang, M. Sutherland, K.S. Wells, T. Yang, P. Yang, J. R. Balser, and D. M. Roden Cardiac-enriched LIM domain protein fhl2 is required to generate IKs in a heterologous system Cardiovasc Res, October 1, 2002; 56(1): 93 - 103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. McLoughlin, E. Ehler, G. Carlile, J. D. Licht, and B. W. Schafer The LIM-only Protein DRAL/FHL2 Interacts with and Is a Corepressor for the Promyelocytic Leukemia Zinc Finger Protein J. Biol. Chem., September 27, 2002; 277(40): 37045 - 37053. [Abstract] [Full Text] [PDF]
|
|