Gu Ruonan, Wang Jerry, Morin Julianne, Lu Aizhu, Liang Wenbin
Cardiac Electrophysiology Laboratory, University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7, Canada.
Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
Biomolecules. 2024 Dec 20;14(12):1639. doi: 10.3390/biom14121639.
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 (, and ) after treatment with 1, 3, or 10 µM of CHIR-99021, an activator of Wnt/β-catenin signaling. CHIR induced similar changes in 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 and transcripts than cells in a low-glucose medium. In addition, a low concentration of CHIR (1 µM) reduced the 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 transcript upregulation and transcript downregulation in CIHR-treated NRVMs. These data suggest that high glucose sensitizes both male and female cardiomyocytes to Wnt/β-catenin signaling.
Wnt/β-连环蛋白信号通路已被证明可调节心肌细胞中的基因表达。然而，尚不清楚这种作用是否取决于细胞的性别或培养基中的葡萄糖水平。在本研究中，从雄性和雌性新生大鼠制备心室肌细胞，并将其维持在富含葡萄糖（25 mM）的培养基或低糖（3 mM）、富含脂质的培养基中。使用实时定量PCR来测量在用1、3或10 μM的CHIR-99021（一种Wnt/β-连环蛋白信号通路激活剂）处理后靶基因（、和）的变化。CHIR在两种培养基中对雄性和雌性新生大鼠心室肌细胞（NRVMs）的转录本诱导了相似的变化，表明不存在性别差异。然而，高糖培养基中的细胞与低糖培养基中的细胞相比，和转录本的增加幅度更大。此外，低浓度的CHIR（1 μM）降低了高糖培养基中细胞的转录本，但在低糖培养基中没有，这表明高糖增加了对Wnt信号的敏感性。在CHIR处理的NRVMs中，转录本上调与转录本下调之间存在非线性关系。这些数据表明，高糖使雄性和雌性心肌细胞对Wnt/β-连环蛋白信号通路敏感。
