Biopolym. Cell. 2016; 32(2):150-157.
http://dx.doi.org/10.7124/bc.000918
Bioinformatics
A link between β-catenin and hypertrophy: evaluation and meta-analysis
1Palchevska O. L., 1Macewicz L. L., 1Piven O. O.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680

Abstract

Heart is a terminally differentiated organ almost unable to regenerate. The remodeling and hypertrophic growth are believed to be the main mechanisms of heart renovation after workloads or injury. Although there have been major advances in the identification of the genes and signaling pathways involved in mediating hypertrophy, further characterization of the underlying molecular mechanisms is needed due to the overall complexity of this process. Aim. The present work is an attempt to systematically assess the previous research on a β-catenin role in the heart muscle hypertrophy development. We hypothesized that β-catenin is a member of universal and conserved regulatory pathway for different tissues and species. To test this hypothesis, we performed the meta-analysis of experimental data available in different databases. Methods. The literature data were analyzed via Origin 8.0 using the simple regression and two-way ANOVA methods. Results. The results allowed selecting the most reproducible hypertrophy markers which were appropriate for the study of β-catenin function in the hypertrophy response (SERCA, actin DIF, Axin-2, c-myc, CD1, BNP, ANP and total protein/DNA index). The analysis shows that a decrease in the β-catenin expression has an ambiguous effect on heart hypertrophy. Conclusion. We have drawn interesting conclusions on the model and species-specific link between the β-catenin level and hypertrophy development, as well as between some hypertrophic markers and β-catenin expression on one hand, and hypertrophy development etc. on the other hand. The results also allowed selecting the most reproducible hypertrophy markers.
Keywords: β-catenin, hypertrophy, heart, meta-analysis, linear regression
Full text: (PDF, in English)

References

[1] Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2-e220.
[2] Brade T, Männer J, Kühl M. The role of Wnt signalling in cardiac development and tissue remodelling in the mature heart. Cardiovasc Res. 2006;72(2):198-209.
[3] Grigoryan T, Wend P, Klaus A, Birchmeier W. Deciphering the function of canonical Wnt signals in development and disease: conditional loss- and gain-of-function mutations of beta-catenin in mice. Genes Dev. 2008;22(17):2308-41.
[4] Nadal-Ginard B, Kajstura J, Leri A, Anversa P. Myocyte death, growth, and regeneration in cardiac hypertrophy and failure. Circ Res. 2003;92(2):139-50.
[5] Ozhan G, Weidinger G. Wnt/β-catenin signaling in heart regeneration. Cell Regen (Lond). 2015;4(1):3.
[6] ter Horst P, Smits JF, Blankesteijn WM. The Wnt/Frizzled pathway as a therapeutic target for cardiac hypertrophy: where do we stand? Acta Physiol (Oxf). 2012;204(1):110-7.
[7] Qu J, Zhou J, Yi XP, Dong B, Zheng H, Miller LM, Wang X, Schneider MD, Li F. Cardiac-specific haploinsufficiency of beta-catenin attenuates cardiac hypertrophy but enhances fetal gene expression in response to aortic constriction. J Mol Cell Cardiol. 2007;43(3):319-26.
[8] Swope D, Cheng L, Gao E, Li J, Radice GL. Loss of cadherin-binding proteins β-catenin and plakoglobin in the heart leads to gap junction remodeling and arrhythmogenesis. Mol Cell Biol. 2012;32(6):1056-67.
[9] Hirschy A, Croquelois A, Perriard E, Schoenauer R, Agarkova I, Hoerstrup SP, Taketo MM, Pedrazzini T, Perriard JC, Ehler E. Stabilised beta-catenin in postnatal ventricular myocardium leads to dilated cardiomyopathy and premature death. Basic Res Cardiol. 2010;105(5):597-608.
[10] Mak KK, Chen MH, Day TF, Chuang PT, Yang Y. Wnt/beta-catenin signaling interacts differentially with Ihh signaling in controlling endochondral bone and synovial joint formation. Development. 2006;133(18):3695-707.
[11] Baurand A, Zelarayan L, Betney R, Gehrke C, Dunger S, Noack C, Busjahn A, Huelsken J, Taketo MM, Birchmeier W, Dietz R, Bergmann MW. Beta-catenin downregulation is required for adaptive cardiac remodeling. Circ Res. 2007;100(9):1353–62.
[12] Bergmann MW. WNT signaling in adult cardiac hypertrophy and remodeling: lessons learned from cardiac development. Circ Res. 2010;107(10):1198-208.
[13] Piven' OO, Pal'chevs'ka OL, Lukash LL. [The Wnt/beta-catenin signaling in embryonic cardiogenesis, postnatal development and myocardium reconstruction]. Tsitol Genet. 2014;48(5):72-83.
[14] Wang Q, Lin JL, Wu KH, Wang DZ, Reiter RS, Sinn HW, Lin CI, Lin CJ. Xin proteins and intercalated disc maturation, signaling and diseases. Front Biosci (Landmark Ed). 2012;17:2566-93.
[15] Jia H, King IN, Chopra SS, Wan H, Ni TT, Jiang C, Guan X, Wells S, Srivastava D, Zhong TP. Vertebrate heart growth is regulated by functional antagonism between Gridlock and Gata5. Proc Natl Acad Sci U S A. 2007;104(35):14008-13.
[16] Jia H, King IN, Chopra SS, Wan H, Ni TT, Jiang C, Guan X, Wells S, Srivastava D, Zhong TP. Vertebrate heart growth is regulated by functional antagonism between Gridlock and Gata5. Proc Natl Acad Sci U S A. 2007;104(35):14008-13.
[17] Buikema JW, Zwetsloot P-PM, Doevendans PA, Domian IJ, Sluijter JPG. Wnt/β-catenin signaling during cardiac development and repair. J Cardiovasc Dev Dis. 2014;1(1):98–110.
[18] Malekar P, Hagenmueller M, Anyanwu A, Buss S, Streit MR, Weiss CS, Wolf D, Riffel J, Bauer A, Katus HA, Hardt SE. Wnt signaling is critical for maladaptive cardiac hypertrophy and accelerates myocardial remodeling. Hypertension. 2010;55(4):939-45.
[19] Palchevska OL, Balatskii VV, Andrejeva AO, Macewicz LL, Piven OO, Lukash LL. Embryonically induced β-catenin haploinsufficiency attenuates postnatal heart development and causes violation of foetal genes program. Biopolym Cell. 2013; 29(2): 124–30.
[20] van de Schans VA, Smits JF, Blankesteijn WM. The Wnt/frizzled pathway in cardiovascular development and disease: friend or foe? Eur J Pharmacol. 2008;585(2-3):338-45.
[21] Marinou K, Christodoulides C, Antoniades C, Koutsilieris M. Wnt signaling in cardiovascular physiology. Trends Endocrinol Metab. 2012;23(12):628-36.