High Glucose Sensitizes Male and Female Rat Cardiomyocytes to Wnt/β-Catenin Signaling

Wnt/β-catenin signaling has been shown to regulate gene expressions in cardiomyocytes. However, it is not known if this effect is dependent on the sex of cells or the glucose level in the culture medium. In the present study, ventricular myocytes were prepared from male and female neonatal rats and...

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Main Authors: Ruonan Gu, Jerry Wang, Julianne Morin, Aizhu Lu, Wenbin Liang
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/14/12/1639
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author Ruonan Gu
Jerry Wang
Julianne Morin
Aizhu Lu
Wenbin Liang
author_facet Ruonan Gu
Jerry Wang
Julianne Morin
Aizhu Lu
Wenbin Liang
author_sort Ruonan Gu
collection DOAJ
description Wnt/β-catenin signaling has been shown to regulate gene expressions in cardiomyocytes. However, it is not known if this effect is dependent on the sex of cells or the glucose level in the culture medium. In the present study, ventricular myocytes were prepared from male and female neonatal rats and maintained in either a glucose-rich (25 mM) medium or a low-glucose (3 mM), lipid-rich medium. Real-time quantitative PCR was used to measure changes in target genes (<i>Axin2</i>, <i>Scn5a,</i> and <i>Tbx3</i>) after treatment with 1, 3, or 10 µM of CHIR-99021, an activator of Wnt/β-catenin signaling. CHIR induced similar changes in <i>Axin2, Tbx3, and Scn5a</i> transcripts in male and female NRVMs in both media, suggesting the absence of sex difference. However, cells in a high-glucose medium showed greater increases in <i>Axin2</i> and <i>Tbx3</i> transcripts than cells in a low-glucose medium. In addition, a low concentration of CHIR (1 µM) reduced the <i>Scn5a</i> transcript in cells in a high-glucose medium but not in a low-glucose medium, suggesting an increased sensitivity to Wnt signaling by high glucose. A non-linear relationship was identified between <i>Axin2</i> transcript upregulation and <i>Scn5a</i> transcript downregulation in CIHR-treated NRVMs. These data suggest that high glucose sensitizes both male and female cardiomyocytes to Wnt/β-catenin signaling.
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spelling doaj-art-efc60f6520354e2a93b0700a7ac65a962024-12-27T14:14:01ZengMDPI AGBiomolecules2218-273X2024-12-011412163910.3390/biom14121639High Glucose Sensitizes Male and Female Rat Cardiomyocytes to Wnt/β-Catenin SignalingRuonan Gu0Jerry Wang1Julianne Morin2Aizhu Lu3Wenbin Liang4Cardiac Electrophysiology Laboratory, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7, CanadaCardiac Electrophysiology Laboratory, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7, CanadaCardiac Electrophysiology Laboratory, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7, CanadaCardiac Electrophysiology Laboratory, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7, CanadaCardiac Electrophysiology Laboratory, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7, CanadaWnt/β-catenin signaling has been shown to regulate gene expressions in cardiomyocytes. However, it is not known if this effect is dependent on the sex of cells or the glucose level in the culture medium. In the present study, ventricular myocytes were prepared from male and female neonatal rats and maintained in either a glucose-rich (25 mM) medium or a low-glucose (3 mM), lipid-rich medium. Real-time quantitative PCR was used to measure changes in target genes (<i>Axin2</i>, <i>Scn5a,</i> and <i>Tbx3</i>) after treatment with 1, 3, or 10 µM of CHIR-99021, an activator of Wnt/β-catenin signaling. CHIR induced similar changes in <i>Axin2, Tbx3, and Scn5a</i> transcripts in male and female NRVMs in both media, suggesting the absence of sex difference. However, cells in a high-glucose medium showed greater increases in <i>Axin2</i> and <i>Tbx3</i> transcripts than cells in a low-glucose medium. In addition, a low concentration of CHIR (1 µM) reduced the <i>Scn5a</i> transcript in cells in a high-glucose medium but not in a low-glucose medium, suggesting an increased sensitivity to Wnt signaling by high glucose. A non-linear relationship was identified between <i>Axin2</i> transcript upregulation and <i>Scn5a</i> transcript downregulation in CIHR-treated NRVMs. These data suggest that high glucose sensitizes both male and female cardiomyocytes to Wnt/β-catenin signaling.https://www.mdpi.com/2218-273X/14/12/1639Wnt signalingcardiac sodium channelScn5aglucose-rich medium
spellingShingle Ruonan Gu
Jerry Wang
Julianne Morin
Aizhu Lu
Wenbin Liang
High Glucose Sensitizes Male and Female Rat Cardiomyocytes to Wnt/β-Catenin Signaling
Biomolecules
Wnt signaling
cardiac sodium channel
Scn5a
glucose-rich medium
title High Glucose Sensitizes Male and Female Rat Cardiomyocytes to Wnt/β-Catenin Signaling
title_full High Glucose Sensitizes Male and Female Rat Cardiomyocytes to Wnt/β-Catenin Signaling
title_fullStr High Glucose Sensitizes Male and Female Rat Cardiomyocytes to Wnt/β-Catenin Signaling
title_full_unstemmed High Glucose Sensitizes Male and Female Rat Cardiomyocytes to Wnt/β-Catenin Signaling
title_short High Glucose Sensitizes Male and Female Rat Cardiomyocytes to Wnt/β-Catenin Signaling
title_sort high glucose sensitizes male and female rat cardiomyocytes to wnt β catenin signaling
topic Wnt signaling
cardiac sodium channel
Scn5a
glucose-rich medium
url https://www.mdpi.com/2218-273X/14/12/1639
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AT juliannemorin highglucosesensitizesmaleandfemaleratcardiomyocytestowntbcateninsignaling
AT aizhulu highglucosesensitizesmaleandfemaleratcardiomyocytestowntbcateninsignaling
AT wenbinliang highglucosesensitizesmaleandfemaleratcardiomyocytestowntbcateninsignaling