open access

Vol 24, No 2 (2017)
Original articles — Basic science and experimental cardiology
Published online: 2016-10-11
Get Citation

Enhancement of beta-catenin in cardiomyocytes suppresses survival protein expression but promotes apoptosis and fibrosis

James C. Lin, Wei-Wen Kuo, Rathinasamy Baskaran, Ming-Cheng Chen, Tsung-Jung Ho, Ray-Jade Chen, Ya-Fang Chen, Viswanadha Vijaya Padma, Ing-Shiow Lay, Chih-Yang Huang
DOI: 10.5603/CJ.a2016.0087
·
Pubmed: 27734460
·
Cardiol J 2017;24(2):195-205.

open access

Vol 24, No 2 (2017)
Original articles — Basic science and experimental cardiology
Published online: 2016-10-11

Abstract

Background: Beta-catenin has been implicated in cell-cell communication in a wide variety of developmental and physiological processes. Defective Wnt signaling could result in various cardiac and vascular abnormalities. Little is known regarding Wnt/frizzled pathway in cardiomyocyte apoptosis.

Methods: In this study, the role of b-catenin in apoptosis was investigated in H9c2 cardiomyocytes and primary cardiomyocytes isolated in diabetic Wistar rats. The cardiomyocytes were transfected with porcine cytomegalovirus (pCMV)-b-catenin plasmid in order to overexpress b-catenin.

Results: The transcription factor displayed a significant nuclear localization in Wistar rats with cardiac hypertension. Transfection of b-catenin plasmid induced apoptosis and reduced expression of survival pathway markers in cardiomyocytes in a dose-dependent manner. Furthermore, expression of fibrosis protein markers was upregulated by the overexpression. Conclusions: Taken together, these results revealed that altered Wnt/b-catenin signaling might provoke heart failure. (Cardiol J 2017; 24, 2: 195–205)

Abstract

Background: Beta-catenin has been implicated in cell-cell communication in a wide variety of developmental and physiological processes. Defective Wnt signaling could result in various cardiac and vascular abnormalities. Little is known regarding Wnt/frizzled pathway in cardiomyocyte apoptosis.

Methods: In this study, the role of b-catenin in apoptosis was investigated in H9c2 cardiomyocytes and primary cardiomyocytes isolated in diabetic Wistar rats. The cardiomyocytes were transfected with porcine cytomegalovirus (pCMV)-b-catenin plasmid in order to overexpress b-catenin.

Results: The transcription factor displayed a significant nuclear localization in Wistar rats with cardiac hypertension. Transfection of b-catenin plasmid induced apoptosis and reduced expression of survival pathway markers in cardiomyocytes in a dose-dependent manner. Furthermore, expression of fibrosis protein markers was upregulated by the overexpression. Conclusions: Taken together, these results revealed that altered Wnt/b-catenin signaling might provoke heart failure. (Cardiol J 2017; 24, 2: 195–205)

Get Citation

Keywords

apoptosis, b-catenin, cardiomyocytes, fibrosis, survival pathway

About this article
Title

Enhancement of beta-catenin in cardiomyocytes suppresses survival protein expression but promotes apoptosis and fibrosis

Journal

Cardiology Journal

Issue

Vol 24, No 2 (2017)

Pages

195-205

Published online

2016-10-11

DOI

10.5603/CJ.a2016.0087

Pubmed

27734460

Bibliographic record

Cardiol J 2017;24(2):195-205.

Keywords

apoptosis
b-catenin
cardiomyocytes
fibrosis
survival pathway

Authors

James C. Lin
Wei-Wen Kuo
Rathinasamy Baskaran
Ming-Cheng Chen
Tsung-Jung Ho
Ray-Jade Chen
Ya-Fang Chen
Viswanadha Vijaya Padma
Ing-Shiow Lay
Chih-Yang Huang

References (47)
  1. Huang CY, Lee SD. Possible pathophysiology of heart failure in obesity: Cardiac apoptosis. BioMedicine. 2012; 2(1): 36–40.
  2. Messaoudi S, Azibani F, Delcayre C, et al. Aldosterone, mineralocorticoid receptor, and heart failure. Mol Cell Endocrinol. 2012; 350(2): 266–272.
  3. Soltysinska E, Olesen SP, Osadchii OE. Myocardial structural, contractile and electrophysiological changes in the guinea-pig heart failure model induced by chronic sympathetic activation. Exp Physiol. 2011; 96(7): 647–663.
  4. Talan MI, Ahmet I, Xiao RP, et al. β₂ AR agonists in treatment of chronic heart failure: long path to translation. J Mol Cell Cardiol. 2011; 51(4): 529–533.
  5. Yin WH, Chen YH, Wei J, et al. Associations between endothelin-1 and adiponectin in chronic heart failure. Cardiology. 2011; 118(4): 207–216.
  6. Distefano G, Sciacca P. Molecular pathogenesis of myocardial remodeling and new potential therapeutic targets in chronic heart failure. Ital J Pediatr. 2012; 38: 41.
  7. Lin WY, Liu HP, Chang JS, et al. Genetic variations within the PSORS1 region affect Kawasaki disease development and coronary artery aneurysm formation. BioMedicine. 2013; 3(2): 73–81.
  8. Palomeque J, Delbridge L, Petroff MV. Angiotensin II: a regulator of cardiomyocyte function and survival. Front Biosci (Landmark Ed). 2009; 14: 5118–5133.
  9. Shah AM, Mann DL. In search of new therapeutic targets and strategies for heart failure: recent advances in basic science. Lancet. 2011; 378(9792): 704–712.
  10. Cooper G. Cardiocyte adaptation to chronically altered load. Annu Rev Physiol. 1987; 49: 501–518.
  11. Mondry A, Swynghedauw B. Biological adaptation of the myocardium to chronic mechanical overload. Molecular determinants of the autonomic nervous system. Eur Heart J. 1995; 16 Suppl I: 64–73.
  12. Ruwhof C, van der Laarse A. Mechanical stress-induced cardiac hypertrophy: mechanisms and signal transduction pathways. Cardiovasc Res. 2000; 47(1): 23–37.
  13. Diwan A, Dorn GW. Decompensation of cardiac hypertrophy: cellular mechanisms and novel therapeutic targets. Physiology (Bethesda). 2007; 22: 56–64.
  14. van de Schans VAM, Smits JFM, Blankesteijn WM. The Wnt/frizzled pathway in cardiovascular development and disease: friend or foe? Eur J Pharmacol. 2008; 585(2-3): 338–345.
  15. ter Horst P, Smits JFM, Blankesteijn WM. The Wnt/Frizzled pathway as a therapeutic target for cardiac hypertrophy: where do we stand? Acta Physiol (Oxf). 2012; 204(1): 110–117.
  16. Kim K, Pang KM, Evans M, et al. Overexpression of beta-catenin induces apoptosis independent of its transactivation function with LEF-1 or the involvement of major G1 cell cycle regulators. Mol Biol Cell. 2000; 11(10): 3509–3523.
  17. Olmeda D, Castel S, Vilaró S, et al. Beta-catenin regulation during the cell cycle: implications in G2/M and apoptosis. Mol Biol Cell. 2003; 14(7): 2844–2860.
  18. Zhang Z, Deb A, Zhang Z, et al. Secreted frizzled related protein 2 protects cells from apoptosis by blocking the effect of canonical Wnt3a. J Mol Cell Cardiol. 2009; 46(3): 370–377.
  19. Zheng Q, Chen P, Xu Z, et al. Expression and redistribution of β-catenin in the cardiac myocytes of left ventricle of spontaneously hypertensive rat. J Mol Histol. 2013; 44(5): 565–573.
  20. Deb A. Cell-cell interaction in the heart via Wnt/β-catenin pathway after cardiac injury. Cardiovasc Res. 2014; 102(2): 214–223.
  21. Pon YL, Wong AST. Gonadotropin-induced apoptosis in human ovarian surface epithelial cells is associated with cyclooxygenase-2 up-regulation via the beta-catenin/T-cell factor signaling pathway. Mol Endocrinol. 2006; 20(12): 3336–3350.
  22. Jüllig M, Zhang WV, Ferreira A, et al. MG132 induced apoptosis is associated with p53-independent induction of pro-apoptotic Noxa and transcriptional activity of beta-catenin. Apoptosis. 2006; 11(4): 627–641.
  23. Akhmetshina A, Palumbo K, Dees C, et al. Activation of canonical Wnt signalling is required for TGF-β-mediated fibrosis. Nat Commun. 2012; 3: 735.
  24. Dawson K, Aflaki M, Nattel S. Role of the Wnt-Frizzled system in cardiac pathophysiology: a rapidly developing, poorly understood area with enormous potential. J Physiol. 2013; 591(6): 1409–1432.
  25. Henderson WR, Chi EY, Ye X, et al. Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis. Proc Natl Acad Sci U S A. 2010; 107(32): 14309–14314.
  26. He W, Dai C, Li Y, et al. Wnt/beta-catenin signaling promotes renal interstitial fibrosis. J Am Soc Nephrol. 2009; 20(4): 765–776.
  27. Laeremans H, Rensen SS, Ottenheijm HCJ, et al. Wnt/frizzled signalling modulates the migration and differentiation of immortalized cardiac fibroblasts. Cardiovasc Res. 2010; 87(3): 514–523.
  28. Ye Bo, Ge Y, Perens G, et al. Canonical Wnt/β-catenin signaling in epicardial fibrosis of failed pediatric heart allografts with diastolic dysfunction. Cardiovasc Pathol. 2013; 22(1): 54–57.
  29. Guo Z, Xia Z, Yuen VG, et al. Cardiac expression of adiponectin and its receptors in streptozotocin-induced diabetic rats. Metabolism. 2007; 56(10): 1363–1371.
  30. Kanter M, Aksu F, Takir M, et al. Effects of Low Intensity Exercise Against Apoptosis and Oxidative Stress in Streptozotocin-induced Diabetic Rat Heart. Exp Clin Endocrinol Diabetes. 2016 [Epub ahead of print].
  31. Wu KK, Huan YM. Streptozotocin-induced diabetic models in mice and rats. . Curr Protoc Pharmacol. 2008: 5.47.1–5.47.14.
  32. Liu X, Liu C, Li J, et al. Urocortin attenuates myocardial fibrosis in diabetic rats via the Akt/GSK-3β signaling pathway. Endocr Res. 2016; 41(2): 148–157.
  33. Diez J, Fortuno MA, Ravassa S. Apoptosis in hypertensive heart disease. Curr Opin Cardiol. 1998; 130: 317–325.
  34. Fortuño MA, Ravassa S, Fortuño A, et al. Cardiomyocyte apoptotic cell death in arterial hypertension: mechanisms and potential management. Hypertension. 2001; 38(6): 1406–1412.
  35. Flaherty M, Dawn B. Noncanonical Wnt11 signaling and cardiomyogenic differentiation. Trends Cardiovasc Med. 2008; 18(7): 260–268.
  36. Pandey S. Targeting Wnt-Frizzled signaling in cardiovascular diseases. Mol Biol Rep. 2013; 40(10): 6011–6018.
  37. Vanderschuren KLA, Sieverink T, Wilders R. Arrhythmogenic right ventricular dysplasia/cardiomyopathy type 1: a light on molecular mechanisms. Genet Res Int. 2013; 2013: 460805.
  38. Tian YC, Phillips AO. Interaction between the transforming growth factor-beta type II receptor/Smad pathway and beta-catenin during transforming growth factor-beta1-mediated adherens junction disassembly. Am J Pathol. 2002; 160(5): 1619–1628.
  39. Guo Y, Xiao L, Sun L, et al. Wnt/beta-catenin signaling: a promising new target for fibrosis diseases. Physiol Res. 2012; 61(4): 337–346.
  40. Mallat Z, Tedgui A, Fontaliran F, et al. Evidence of apoptosis in arrhythmogenic right ventricular dysplasia. N Engl J Med. 1996; 335(16): 1190–1196.
  41. Yamaji K, Fujimoto S, Ikeda Y, et al. Apoptotic myocardial cell death in the setting of arrhythmogenic right ventricular cardiomyopathy. Acta Cardiol. 2005; 60(5): 465–470.
  42. Hanna C, Hubchak SC, Liang X, et al. Hypoxia-inducible factor-2α and TGF-β signaling interact to promote normoxic glomerular fibrogenesis. Am J Physiol Renal Physiol. 2013; 305(9): F1323–F1331.
  43. Hung SP, Yang MH, Tseng KF, et al. Hypoxia-induced secretion of TGF-β1 in mesenchymal stem cell promotes breast cancer cell progression. Cell Transplant. 2013; 22(10): 1869–1882.
  44. Suzuki YJ. Cell signaling pathways for the regulation of GATA4 transcription factor: Implications for cell growth and apoptosis. Cell Signal. 2011; 23(7): 1094–1099.
  45. Jian H, Shen X, Liu I, et al. Smad3-dependent nuclear translocation of beta-catenin is required for TGF-beta1-induced proliferation of bone marrow-derived adult human mesenchymal stem cells. Genes Dev. 2006; 20(6): 666–674.
  46. Zhou B, Liu Y, Kahn M, et al. Interactions between β-catenin and transforming growth factor-β signaling pathways mediate epithelial-mesenchymal transition and are dependent on the transcriptional co-activator cAMP-response element-binding protein (CREB)-binding protein (CBP). J Biol Chem. 2012; 287(10): 7026–7038.
  47. Zhou S. TGF-β regulates β-catenin signaling and osteoblast differentiation in human mesenchymal stem cells. J Cell Biochem. 2011; 112(6): 1651–1660.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk, Poland
tel.:+48 58 320 94 94, fax:+48 58 320 94 60, e-mail: viamedica@viamedica.pl