YB-1 Is a Novel Target for the Inhibition of α-Adrenergic-Induced Hypertrophy
Cardiac hypertrophy resulting from sympathetic nervous system activation triggers the development of heart failure. The transcription factor Y-box binding protein 1 (YB-1) can interact with transcription factors involved in cardiac hypertrophy and may thereby interfere with the hypertrophy growth pr...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/1/401 |
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| author | Jacqueline Heger Stefan Partsch Claudia Harjung Zoltán V. Varga Tamás Baranyai Johannes Weiß Lea Kremer Fabian Locquet Przemyslaw Leszek Bence Ágg Bettina Benczik Péter Ferdinandy Rainer Schulz Gerhild Euler |
| author_facet | Jacqueline Heger Stefan Partsch Claudia Harjung Zoltán V. Varga Tamás Baranyai Johannes Weiß Lea Kremer Fabian Locquet Przemyslaw Leszek Bence Ágg Bettina Benczik Péter Ferdinandy Rainer Schulz Gerhild Euler |
| author_sort | Jacqueline Heger |
| collection | DOAJ |
| description | Cardiac hypertrophy resulting from sympathetic nervous system activation triggers the development of heart failure. The transcription factor Y-box binding protein 1 (YB-1) can interact with transcription factors involved in cardiac hypertrophy and may thereby interfere with the hypertrophy growth process. Therefore, the question arises as to whether YB-1 influences cardiomyocyte hypertrophy and might thereby influence the development of heart failure. YB-1 expression is downregulated in human heart biopsies of patients with ischemic cardiomyopathy (<i>n</i> = 8), leading to heart failure. To study the impact of reduced YB-1 in cardiac cells, we performed small interfering RNA (siRNA) experiments in H9C2 cells as well as in adult cardiomyocytes (CMs) of rats. The specificity of YB-1 siRNA was analyzed by a miRNA-like off-target prediction assay identifying potential genes. Testing three high-scoring genes by transfecting cardiac cells with YB-1 siRNA did not result in downregulation of these genes in contrast to <i>YB-1</i>, whose downregulation increased hypertrophic growth. Hypertrophic growth was mediated by PI3K under PE stimulation, as well by downregulation with YB-1 siRNA. On the other hand, overexpression of <i>YB-1</i> in CMs, caused by infection with an adenovirus encoding <i>YB-1</i> (AdYB-1), prevented hypertrophic growth under α-adrenergic stimulation with phenylephrine (PE), but not under stimulation with growth differentiation factor 15 (GDF15; <i>n</i> = 10–16). An adenovirus encoding the green fluorescent protein (AdGFP) served as the control. <i>YB-1</i> overexpression enhanced the mRNA expression of the Gq inhibitor regulator of G-protein signaling 2 (<i>RGS2</i>) under PE stimulation (<i>n</i> = 6), potentially explaining its inhibitory effect on PE-induced hypertrophic growth. This study shows that YB-1 protects cardiomyocytes against PE-induced hypertrophic growth. Like in human end-stage heart failure, YB-1 downregulation may cause the heart to lose its protection against hypertrophic stimuli and progress to heart failure. Therefore, the transcription factor YB-1 is a pivotal signaling molecule, providing perspectives for therapeutic approaches. |
| first_indexed | 2024-03-08T15:05:12Z |
| format | Article |
| id | doaj.art-43a811068dde42149ee976eccc024c5a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T15:05:12Z |
| publishDate | 2023-12-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-43a811068dde42149ee976eccc024c5a2024-01-10T14:59:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0125140110.3390/ijms25010401YB-1 Is a Novel Target for the Inhibition of α-Adrenergic-Induced HypertrophyJacqueline Heger0Stefan Partsch1Claudia Harjung2Zoltán V. Varga3Tamás Baranyai4Johannes Weiß5Lea Kremer6Fabian Locquet7Przemyslaw Leszek8Bence Ágg9Bettina Benczik10Péter Ferdinandy11Rainer Schulz12Gerhild Euler13Institute of Physiology, Justus Liebig University, 35392 Giessen, GermanyInstitute of Physiology, Justus Liebig University, 35392 Giessen, GermanyInstitute of Physiology, Justus Liebig University, 35392 Giessen, GermanyHCEMM-SU Cardiometabolic Immunology Research Group, 1094 Budapest, HungaryCardiometabolic and MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1094 Budapest, HungaryInstitute of Physiology, Justus Liebig University, 35392 Giessen, GermanyInstitute of Physiology, Justus Liebig University, 35392 Giessen, GermanyInstitute of Physiology, Justus Liebig University, 35392 Giessen, GermanyDepartment of Heart Failure and Transplantology, Cardinal Stefan Wyszyński Institute of Cardiology, 04-628 Warszawa, PolandCardiometabolic and MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1094 Budapest, HungaryCardiometabolic and MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1094 Budapest, HungaryCardiometabolic and MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1094 Budapest, HungaryInstitute of Physiology, Justus Liebig University, 35392 Giessen, GermanyInstitute of Physiology, Justus Liebig University, 35392 Giessen, GermanyCardiac hypertrophy resulting from sympathetic nervous system activation triggers the development of heart failure. The transcription factor Y-box binding protein 1 (YB-1) can interact with transcription factors involved in cardiac hypertrophy and may thereby interfere with the hypertrophy growth process. Therefore, the question arises as to whether YB-1 influences cardiomyocyte hypertrophy and might thereby influence the development of heart failure. YB-1 expression is downregulated in human heart biopsies of patients with ischemic cardiomyopathy (<i>n</i> = 8), leading to heart failure. To study the impact of reduced YB-1 in cardiac cells, we performed small interfering RNA (siRNA) experiments in H9C2 cells as well as in adult cardiomyocytes (CMs) of rats. The specificity of YB-1 siRNA was analyzed by a miRNA-like off-target prediction assay identifying potential genes. Testing three high-scoring genes by transfecting cardiac cells with YB-1 siRNA did not result in downregulation of these genes in contrast to <i>YB-1</i>, whose downregulation increased hypertrophic growth. Hypertrophic growth was mediated by PI3K under PE stimulation, as well by downregulation with YB-1 siRNA. On the other hand, overexpression of <i>YB-1</i> in CMs, caused by infection with an adenovirus encoding <i>YB-1</i> (AdYB-1), prevented hypertrophic growth under α-adrenergic stimulation with phenylephrine (PE), but not under stimulation with growth differentiation factor 15 (GDF15; <i>n</i> = 10–16). An adenovirus encoding the green fluorescent protein (AdGFP) served as the control. <i>YB-1</i> overexpression enhanced the mRNA expression of the Gq inhibitor regulator of G-protein signaling 2 (<i>RGS2</i>) under PE stimulation (<i>n</i> = 6), potentially explaining its inhibitory effect on PE-induced hypertrophic growth. This study shows that YB-1 protects cardiomyocytes against PE-induced hypertrophic growth. Like in human end-stage heart failure, YB-1 downregulation may cause the heart to lose its protection against hypertrophic stimuli and progress to heart failure. Therefore, the transcription factor YB-1 is a pivotal signaling molecule, providing perspectives for therapeutic approaches.https://www.mdpi.com/1422-0067/25/1/401Y-box binding protein 1cardiomyocytesH9C2 cellshypertrophy |
| spellingShingle | Jacqueline Heger Stefan Partsch Claudia Harjung Zoltán V. Varga Tamás Baranyai Johannes Weiß Lea Kremer Fabian Locquet Przemyslaw Leszek Bence Ágg Bettina Benczik Péter Ferdinandy Rainer Schulz Gerhild Euler YB-1 Is a Novel Target for the Inhibition of α-Adrenergic-Induced Hypertrophy International Journal of Molecular Sciences Y-box binding protein 1 cardiomyocytes H9C2 cells hypertrophy |
| title | YB-1 Is a Novel Target for the Inhibition of α-Adrenergic-Induced Hypertrophy |
| title_full | YB-1 Is a Novel Target for the Inhibition of α-Adrenergic-Induced Hypertrophy |
| title_fullStr | YB-1 Is a Novel Target for the Inhibition of α-Adrenergic-Induced Hypertrophy |
| title_full_unstemmed | YB-1 Is a Novel Target for the Inhibition of α-Adrenergic-Induced Hypertrophy |
| title_short | YB-1 Is a Novel Target for the Inhibition of α-Adrenergic-Induced Hypertrophy |
| title_sort | yb 1 is a novel target for the inhibition of α adrenergic induced hypertrophy |
| topic | Y-box binding protein 1 cardiomyocytes H9C2 cells hypertrophy |
| url | https://www.mdpi.com/1422-0067/25/1/401 |
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