Transforming Growth Factor Beta (TGF-β1) Induces Pro-Reparative Phenotypic Changes in Epicardial Cells in Mice

doi:10.1007/s10517-021-05107-5

. 2021 Feb;170(4):565-570.

doi: 10.1007/s10517-021-05107-5. Epub 2021 Mar 17.

Transforming Growth Factor Beta (TGF-β1) Induces Pro-Reparative Phenotypic Changes in Epicardial Cells in Mice

K V Dergilev¹, Z I Tsokolaeva^{2

3}, I B Beloglazova², E I Ratner², E V Parfenova^{2

4}

Affiliations

¹ Laboratory of Angiogenesis, Institute of Experimental Cardiology, National Medical Research Centre of Cardiology, Ministry of Health of the Russian Federation, Moscow, Russia. doctorkote@gmail.com.
² Laboratory of Angiogenesis, Institute of Experimental Cardiology, National Medical Research Centre of Cardiology, Ministry of Health of the Russian Federation, Moscow, Russia.
³ V. A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russia.
⁴ Laboratory of Postgenomic Technologies in Medicine, Faculty of Fundamental Medicine, M. V. Lomonosov Moscow State University, Moscow, Russia.

PMID: 33730328
DOI: 10.1007/s10517-021-05107-5

Transforming Growth Factor Beta (TGF-β1) Induces Pro-Reparative Phenotypic Changes in Epicardial Cells in Mice

K V Dergilev et al. Bull Exp Biol Med. 2021 Feb.

. 2021 Feb;170(4):565-570.

doi: 10.1007/s10517-021-05107-5. Epub 2021 Mar 17.

Authors

K V Dergilev¹, Z I Tsokolaeva^{2

3}, I B Beloglazova², E I Ratner², E V Parfenova^{2

4}

Affiliations

¹ Laboratory of Angiogenesis, Institute of Experimental Cardiology, National Medical Research Centre of Cardiology, Ministry of Health of the Russian Federation, Moscow, Russia. doctorkote@gmail.com.
² Laboratory of Angiogenesis, Institute of Experimental Cardiology, National Medical Research Centre of Cardiology, Ministry of Health of the Russian Federation, Moscow, Russia.
³ V. A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russia.
⁴ Laboratory of Postgenomic Technologies in Medicine, Faculty of Fundamental Medicine, M. V. Lomonosov Moscow State University, Moscow, Russia.

PMID: 33730328
DOI: 10.1007/s10517-021-05107-5

Abstract

We evaluated the content of active form of TGF-β1 in the intact and post-infarction heart and the effect of this factor on the properties of epicardial cells. During the acute stage after myocardial infarction, the production of TGF-β1 in the heart increased, which closely correlated with activation of epicardial cells (appearance of a pool of Wt1+ epicardial cells entering the epithelial-mesenchymal transition). The role of TGF-β1 as the factor of epicardial activation was confirmed by the results of in vitro experiments: addition of recombinant TGF-β1 to cultured epicardial cells led to enhanced expression of genes of epithelial-mesenchymal transition and phenotypic transformation of these cells leading to the appearance of cells with markers of smooth muscle cells and fibroblasts. Our findings suggest that the regulatory axis "TGF-β1-epicardium cells" can be considered as an important link of the post-infarction reparative process and adaptive response during heart remodeling after myocardial infarction and as the target for therapeutic interventions.

Keywords: epicardial cells; epithelial-mesenchymal transition; heart repair; myocardial infarction; transforming growth factor beta.

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References

1. Dergilev KV, Komova AV, Tsokolaeva ZI, Beloglazova IB, Parfyonova YeV. Epicardium as a new target for regenerative technologies in cardiology. Geny Kletki. 2020;15(2):33-40. Russian.
1. Dergilev KV, Tsokolaeva ZI, Beloglazova IB, Ratner EI, Molokotina YuD, Parfenova EV. Angiogenic properties of myocardial c-kit⁺ cells. Geny Kletki. 2018;13(3):82-88. Russian.
1. Sergienko IV, Semenova AE, Masenko VP, Habibullina LI Gabrusenko SA, Kukharchuk VV, Belenkov YuN. Myocardial revascularization effects on vascular endothelial growth factor and transforming growth factor β-1 in coronary heart disease patients. Kardiovask. Ter. Prof. 2007;6(5):12-17. Russian.
1. Assoian RK, Fleurdelys BE, Stevenson HC, Miller PJ, Madtes DK, Raines EW, Ross R, Sporn MB. Expression and secretion of type beta transforming growth factor by activated human macrophages. Proc. Natl Acad. Sci. USA. 1987;84(17):6020-6024. - DOI
1. Burns WC, Thomas MC. The molecular mediators of type 2 epithelial to mesenchymal transition (EMT) and their role in renal pathophysiology. Expert Rev. Mol. Med. 2010;12:e17. doi: https://doi.org/10.1017/S1462399410001481 - DOI - PubMed

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[1] Dergilev KV, Komova AV, Tsokolaeva ZI, Beloglazova IB, Parfyonova YeV. Epicardium as a new target for regenerative technologies in cardiology. Geny Kletki. 2020;15(2):33-40. Russian.

[2] Dergilev KV, Komova AV, Tsokolaeva ZI, Beloglazova IB, Parfyonova YeV. Epicardium as a new target for regenerative technologies in cardiology. Geny Kletki. 2020;15(2):33-40. Russian.

[3] Dergilev KV, Tsokolaeva ZI, Beloglazova IB, Ratner EI, Molokotina YuD, Parfenova EV. Angiogenic properties of myocardial c-kit⁺ cells. Geny Kletki. 2018;13(3):82-88. Russian.

[4] Dergilev KV, Tsokolaeva ZI, Beloglazova IB, Ratner EI, Molokotina YuD, Parfenova EV. Angiogenic properties of myocardial c-kit⁺ cells. Geny Kletki. 2018;13(3):82-88. Russian.

[5] Sergienko IV, Semenova AE, Masenko VP, Habibullina LI Gabrusenko SA, Kukharchuk VV, Belenkov YuN. Myocardial revascularization effects on vascular endothelial growth factor and transforming growth factor β-1 in coronary heart disease patients. Kardiovask. Ter. Prof. 2007;6(5):12-17. Russian.

[6] Sergienko IV, Semenova AE, Masenko VP, Habibullina LI Gabrusenko SA, Kukharchuk VV, Belenkov YuN. Myocardial revascularization effects on vascular endothelial growth factor and transforming growth factor β-1 in coronary heart disease patients. Kardiovask. Ter. Prof. 2007;6(5):12-17. Russian.

[7] Assoian RK, Fleurdelys BE, Stevenson HC, Miller PJ, Madtes DK, Raines EW, Ross R, Sporn MB. Expression and secretion of type beta transforming growth factor by activated human macrophages. Proc. Natl Acad. Sci. USA. 1987;84(17):6020-6024. - DOI

[8] Assoian RK, Fleurdelys BE, Stevenson HC, Miller PJ, Madtes DK, Raines EW, Ross R, Sporn MB. Expression and secretion of type beta transforming growth factor by activated human macrophages. Proc. Natl Acad. Sci. USA. 1987;84(17):6020-6024. - DOI

[9] Burns WC, Thomas MC. The molecular mediators of type 2 epithelial to mesenchymal transition (EMT) and their role in renal pathophysiology. Expert Rev. Mol. Med. 2010;12:e17. doi: https://doi.org/10.1017/S1462399410001481 - DOI - PubMed

[10] Burns WC, Thomas MC. The molecular mediators of type 2 epithelial to mesenchymal transition (EMT) and their role in renal pathophysiology. Expert Rev. Mol. Med. 2010;12:e17. doi: https://doi.org/10.1017/S1462399410001481 - DOI - PubMed

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Transforming Growth Factor Beta (TGF-β1) Induces Pro-Reparative Phenotypic Changes in Epicardial Cells in Mice

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Transforming Growth Factor Beta (TGF-β1) Induces Pro-Reparative Phenotypic Changes in Epicardial Cells in Mice

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