Notch1 Is Involved in Physiologic Cardiac Hypertrophy of Mice via the p38 Signaling Pathway after Voluntary Running
Appropriate exercise such as voluntary wheel-running can induce physiological cardiac hypertrophy. Notch1 plays an important role in cardiac hypertrophy; however, the experimental results are inconsistent. In this experiment, we aimed to explore the role of Notch1 in physiological cardiac hypertroph...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/4/3212 |
| Summary: | Appropriate exercise such as voluntary wheel-running can induce physiological cardiac hypertrophy. Notch1 plays an important role in cardiac hypertrophy; however, the experimental results are inconsistent. In this experiment, we aimed to explore the role of Notch1 in physiological cardiac hypertrophy. Twenty-nine adult male mice were randomly divided into a Notch1 heterozygous deficient control (Notch1<sup>+/−</sup> CON) group, a Notch1 heterozygous deficient running (Notch1<sup>+/−</sup> RUN) group, a wild type control (WT CON) group, and a wild type running (WT RUN) group. Mice in the Notch1<sup>+/−</sup> RUN and WT RUN groups had access to voluntary wheel-running for two weeks. Next, the cardiac function of all of the mice was examined by echocardiography. The H&E staining, Masson trichrome staining, and a Western blot assay were carried out to analyze cardiac hypertrophy, cardiac fibrosis, and the expression of proteins relating to cardiac hypertrophy. After two-weeks of running, the Notch1 receptor expression was decreased in the hearts of the WT RUN group. The degree of cardiac hypertrophy in the Notch1<sup>+/−</sup> RUN mice was lower than that of their littermate control. Compared to the Notch1<sup>+/−</sup> CON group, Notch1 heterozygous deficiency could lead to a decrease in Beclin-1 expression and the ratio of LC3II/LC3I in the Notch1<sup>+/−</sup> RUN group. The results suggest that Notch1 heterozygous deficiency could partly dampen the induction of autophagy. Moreover, Notch1 deficiency may lead to the inactivation of p38 and the reduction of β-catenin expression in the Notch1<sup>+/−</sup> RUN group. In conclusion, Notch1 plays a critical role in physiologic cardiac hypertrophy through the p38 signaling pathway. Our results will help to understand the underlying mechanism of Notch1 on physiological cardiac hypertrophy. |
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| ISSN: | 1661-6596 1422-0067 |