Skip to main content
SpringerLink
Log in

Transplantation of mesenchymal stem cells modulated Cx43 and Cx45 expression in rats with myocardial infarction

  • Original Article
  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

At present, little is known about the influence of mesenchymal stem cell (MSC) transplantation on connexin43 (Cx43) and connexin45 (Cx45) remodeling in the ischemic heart. In this study, we investigated the effect of MSC transplantation on Cx43 and Cx45 remodeling in the ischemic heart. Wistar rats were subjected to left anterior descending artery ligation to induce myocardial infarction (MI) and then randomly allocated to receive an intramyocardial injection of PBS (MI group) or 5-azacytidine-induced MSCs (MSCs group). Histological examination and western blotting were performed 4 weeks after cell transplantation. We found that the MSCs exhibited plasticity by differentiating into cardiomyocyte-like cells. Gap junction remodeling after MI was characterized by a decrease in Cx43 expression and an increase in Cx45 expression. MSC transplantation modulated the MI-induced abnormalities by up-regulating Cx43 and down-regulating Cx45 expression. MSCs exhibited plasticity by differentiating into cardiomyocyte-like cells and modulated abnormal Cx43 and Cx45 remodeling following MI.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Alcoléa S, Théveniau-Ruissy M, Jarry-Guichard T, Marics I, Tzouanacou E, Chauvin JP, Briand JP, Moorman AF, Lamers WH, Gros DB (1999) Downregulation of connexin 45 gene products during mouse heart development. Circ Res 84:1365–1379

    Article  Google Scholar 

  • Betsuyaku T, Nnebe NS, Sundset R, Patibandla S, Krueger CM, Yamada KA (2006) Overexpression of cardiac connexin45 increases susceptibility to ventricular tachyarrhythmias in vivo. Am J Physiol Heart Circ Physiol 290:H163–H171

    Article  CAS  Google Scholar 

  • Desplantez T, Dupont E, Severs NJ, Weingart R (2007) Gap junction channels and cardiac impulse propagation. J Membr Biol 218:13–28

    Article  CAS  Google Scholar 

  • Fukuda K (2003) Regeneration of cardiomyocytes from bone marrow: use of mesenchymal stem cell for cardiovascular tissue engineering. Cytotechnology 41:165–175

    Article  CAS  Google Scholar 

  • Goodenough DA, Goliger JA, Paul DL (1996) Connexins, connexons, and intercellular communication. Annu Rev Biochem 65:475–502

    Article  CAS  Google Scholar 

  • Kar R, Batra N, Riquelme MA, Jiang JX (2012) Biological role of connexin intercellular channels and hemichannels. Arch Biochem Biophys 524:2–15

    Article  CAS  Google Scholar 

  • Kostin S, Rieger M, Dammer S, Hein S, Richter M, Klövekorn WP, Bauer EP, Schaper J (2003) Gap junction remodeling and altered connexin43 expression in the failing human heart. Mol Cell Biochem 242:135–144

    Article  CAS  Google Scholar 

  • Li J-Y, He Y, Wen L, Ke HH, Wei Z, Deng Y, Wu ZF (2009a) Effects of allogenic bone marrow mesenchymal stem cell transplantation on electrophysiological abnormality and left ventricular remodeling in rats with myocardial infarction. J Clin Rehabil Tissue Eng Res 13:5211–5216

    Google Scholar 

  • Li J-Y, Zong GQ, Wei Z, Xu WY, Ke HH, Ning Z, Wu ZF (2009b) Establishment of a rat model of myocardial infarction and the post-infarction changes in electrophysiology and left ventricular function. Acta Lab Anim Sci Sin 17:419–423

    Google Scholar 

  • Martinez AD, Hayrapetyan V, Moreno AP, Beyer EC (2002) Connexin 43 and connexin 45 form heteromeric gap junction channels in which individual components determine permeability and regulation. Circ Res 90:1100–1107

    Article  CAS  Google Scholar 

  • Murry CE, Field LJ, Menasché P (2005) Cell-based cardiac repair: reflections at the 10-year point. Circulation 112:3174–3183

    Article  Google Scholar 

  • Peters NS, Coromilas J, Severs NJ, Wit AL (1997) Disturbed connexin43 gap junction distribution correlates with the location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia. Circulation 95:988–996

    Article  CAS  Google Scholar 

  • Qian Q, Qian H, Zhang X, Zhu W, Yan Y, Ye S, Peng X, Li W, Xu Z, Sun L, Xu W (2012) 5-Azacytidine induces cardiac differentiation of human umbilical cord-derived mesenchymal stem cells by activating extracellular regulated kinase. Stem Cells Dev 21:67–75

    Article  CAS  Google Scholar 

  • Roell W, Lewalter T, Sasse P, Tallini YN, Choi BR, Breitbach M, Doran R, Becher UM, Hwang SM, Bostani T, von Maltzahn J, Hofmann A, Reining S, Eiberger B, Gabris B, Pfeifer A, Welz A, Willecke K, Salama G, Schrickel JW, Kotlikoff MI, Fleischmann BK (2007) Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia. Nature 450:819–824

    Article  CAS  Google Scholar 

  • Severs NJ, Coppen SR, Dupont E, Yeh HI, Ko YS, Matsushita T (2004) Gap junction alterations in human cardiac disease. Cardiovasc Res 62:368–377

    Article  CAS  Google Scholar 

  • Smith JH, Green CR, Peters NS, Rothery S, Severs NJ (1991) Altered patterns of gap junction distribution in ischemic heart disease. An immunohistochemical study of human myocardium using laser scanning confocal microscopy. Am J Pathol 139:801–821

    CAS  Google Scholar 

  • Takamatsu T (2008) Arrhythmogenic substrates in myocardial infarct. Pathol Int 58:533–543

    Article  CAS  Google Scholar 

  • Valiunas V, Doronin S, Valiuniene L, Potapova I, Zuckerman J, Walcott B, Robinson RB, Rosen MR, Brink PR, Cohen IS (2004) Human mesenchymal stem cells make cardiac connexins and form functional gap junctions. J Physiol 555:617–626

    Article  CAS  Google Scholar 

  • van der Bogt KE, Sheikh AY, Schrepfer S, Hoyt G, Cao F, Ransohoff KJ, Swijnenburg RJ, Pearl J, Lee A, Fischbein M, Contag CH, Robbins RC, Wu JC (2008) Comparison of different adult stem cell types for treatment of myocardial ischemia. Circulation 118:S121–S129

    Article  Google Scholar 

  • Yamada KA, Rogers JG, Sundset R, Steinberg TH, Saffitz J (2003) Up-regulation of connexin45 in heart failure. J Cardiovasc Electrophysiol 14:1205–1212

    Article  Google Scholar 

  • Zhao YM, Li JY, He Y, Ke HH, Wang DX (2009) mRNA expression of connectin 43 and connectin 45 following transplantation of allogenic bone marrow mesenchymal stem cells in rats with acute myocardial infarction. J Clin Rehab Tissue Eng Res 13:8895–8900

    CAS  Google Scholar 

  • Zhong G, Moreno AP (2002) The formation of mono-heteromeric Cx43-Cx45/43 gap junctions uncovers gating and selectivity properties of their channels. Biophys J 82:633b

    Google Scholar 

Download references

Acknowledgements

We would like to thank Drs. Ying-lin Wu and Jing-bo Jiang for their manuscript edits and revisions.

Funding

This study was supported by the National Natural Science Foundation of China (No. 30560051).

Author information

Author notes

  1. Jin-yi Li and Hong-hong Ke have contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China

    Jin-yi Li, Hong-hong Ke, Yan He, Li-na Wen, Wei-yan Xu, Zhi-fu Wu, Yan-mei Zhao & Guo-qiang Zhong

Authors
  1. Jin-yi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hong-hong Ke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yan He
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Li-na Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei-yan Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhi-fu Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yan-mei Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Guo-qiang Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guo-qiang Zhong.

Ethics declarations

Conflict of interest

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Jy., Ke, Hh., He, Y. et al. Transplantation of mesenchymal stem cells modulated Cx43 and Cx45 expression in rats with myocardial infarction. Cytotechnology 70, 225–234 (2018). https://doi.org/10.1007/s10616-017-0136-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10616-017-0136-x

Keywords

Search

Navigation