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Open AccessArticle

MiR-21, MiR-29a, GATA4, and MEF2c Expression Changes in Endothelin-1 and Angiotensin II Cardiac Hypertrophy Stimulated Isl-1+Sca-1+c-kit+ Porcine Cardiac Progenitor Cells In Vitro

1
Medical University of Vienna, Department of Cardiology, 1090 Vienna, Austria
2
Medical University of Vienna, Department of Biomedical Research, 1090 Vienna, Austria
*
Authors to whom correspondence should be addressed.
Cells 2019, 8(11), 1416; https://doi.org/10.3390/cells8111416 (registering DOI)
Received: 27 September 2019 / Revised: 6 November 2019 / Accepted: 7 November 2019 / Published: 9 November 2019
(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)
Cost- and time-intensive porcine translational disease models offer great opportunities to test drugs and therapies for pathological cardiac hypertrophy and can be supported by porcine cell culture models that provide further insights into basic disease mechanisms. Cardiac progenitor cells (CPCs) residing in the adult heart have been shown to differentiate in vitro into cardiomyocytes and could contribute to cardiac regeneration. Therefore, it is important to evaluate their changes on the cellular level caused by disease. We successfully isolated Isl1+Sca1+cKit+ porcine CPCs (pCPCs) from pig hearts and stimulated them with endothelin-1 (ET-1) and angiotensin II (Ang II) in vitro. We also performed a cardiac reprogramming transfection and tested the same conditions. Our results show that undifferentiated Isl1+Sca1+cKit+ pCPCs were significantly upregulated in GATA4, MEF2c, and miR-29a gene expressions and in BNP and MCP-1 protein expressions with Ang II stimulation, but they showed no significant changes in miR-29a and MCP-1 when stimulated with ET-1. Differentiated Isl1+Sca1+cKit+ pCPCs exhibited significantly higher levels of MEF2c, GATA4, miR-29a, and miR-21 as well as Cx43 and BNP with Ang II stimulation. pMx-MGT-transfected Isl1+Sca1+cKit+ pCPCs showed significant elevations in MEF2c, GATA4, and BNP expressions when stimulated with ET-1. Our model demonstrates that in vitro stimulation leads to successful Isl1+Sca1+cKit+ pCPC hypertrophy with upregulation of cardiac remodeling associated genes and profibrotic miRNAs and offers great possibilities for further investigations of disease mechanisms and treatment. View Full-Text
Keywords: porcine cardiac progenitor cells; cardiac hypertrophy; cardiac remodeling; Isl-1; angiotensin II; endothelin 1; MEF2c; GATA4; miR-21; miR29a porcine cardiac progenitor cells; cardiac hypertrophy; cardiac remodeling; Isl-1; angiotensin II; endothelin 1; MEF2c; GATA4; miR-21; miR29a
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Zlabinger, K.; Spannbauer, A.; Traxler, D.; Gugerell, A.; Lukovic, D.; Winkler, J.; Mester-Tonczar, J.; Podesser, B.; Gyöngyösi, M. MiR-21, MiR-29a, GATA4, and MEF2c Expression Changes in Endothelin-1 and Angiotensin II Cardiac Hypertrophy Stimulated Isl-1+Sca-1+c-kit+ Porcine Cardiac Progenitor Cells In Vitro. Cells 2019, 8, 1416.

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