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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+\/\u2212 CON) group, a Notch1 heterozygous deficient running (Notch1+\/\u2212 RUN) group, a wild type control (WT CON) group, and a wild type running (WT RUN) group. Mice in the Notch1+\/\u2212 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&amp;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+\/\u2212 RUN mice was lower than that of their littermate control. Compared to the Notch1+\/\u2212 CON group, Notch1 heterozygous deficiency could lead to a decrease in Beclin-1 expression and the ratio of LC3II\/LC3I in the Notch1+\/\u2212 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 \u03b2-catenin expression in the Notch1+\/\u2212 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.<\/jats:p>","DOI":"10.3390\/ijms24043212","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T01:56:48Z","timestamp":1675735008000},"page":"3212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Notch1 Is Involved in Physiologic Cardiac Hypertrophy of Mice via the p38 Signaling Pathway after Voluntary Running"],"prefix":"10.3390","volume":"24","author":[{"given":"Weiwei","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Medicine, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6590-1289","authenticated-orcid":false,"given":"Jiayi","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zekang","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanwei","family":"Fan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhua","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"899","DOI":"10.3389\/fphys.2017.00899","article-title":"Voluntary exercise improves cardiac function and prevents cardiac remodeling in a mouse model of dilated cardiomyopathy","volume":"8","author":"Deloux","year":"2017","journal-title":"Front. 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