CDX1 improves nicotine induced cardiac fibroblasts activation and cardiomyocyte hypertrophy by alleviating autophagic flux impairment through modulation of LAPTM4B
Abstract Nicotine-induced impairment of autophagic flux promotes the onset of myocardial remodelling, thereby exacerbating heart failure. In this study, we investigated the role and molecular mechanisms of the transcription factor CDX1 in cardiac fibroblasts (CFs) activation and cardiomyocyte hypert...
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Nature Portfolio
2025-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-94160-5 |
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| author | Yue-yan Li Fan-liang Meng Si-yuan Zhou Jia-min Du Wen-jing Li Qi-yun Liu Lei Wu Meng-meng Zhao Yi Jin Qun-ye Zhang Ying Li Guo-hai Su |
| author_facet | Yue-yan Li Fan-liang Meng Si-yuan Zhou Jia-min Du Wen-jing Li Qi-yun Liu Lei Wu Meng-meng Zhao Yi Jin Qun-ye Zhang Ying Li Guo-hai Su |
| author_sort | Yue-yan Li |
| collection | DOAJ |
| description | Abstract Nicotine-induced impairment of autophagic flux promotes the onset of myocardial remodelling, thereby exacerbating heart failure. In this study, we investigated the role and molecular mechanisms of the transcription factor CDX1 in cardiac fibroblasts (CFs) activation and cardiomyocyte hypertrophy induced by nicotine. We found that CDX1 expression was increased in response to nicotine. However, a decrease in CDX1 further exacerbated the nicotine-induced blockade of autophagic flux, thereby aggravating CFs activation and cardiomyocyte hypertrophy. This effect was attributed to the suppression of the autophagic regulator LAPTM4B transcription by CDX1 and the subsequent activation of the mTOR pathway. In contrast, CDX1 overexpression promoted LAPTM4B expression, resulting in the opposite effect. In conclusion, our study demonstrated that CDX1/LAPTM4B axis could alleviate nicotine-induced autophagy flux impairment by inhibiting mTORC1 pathway activation, thereby alleviating CFs activation and cardiomyocyte hypertrophy, and exerting cardioprotective functions. |
| format | Article |
| id | doaj-art-1cea9fa7c68d44f4a8ad5e922c15908a |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-1cea9fa7c68d44f4a8ad5e922c15908a2025-08-20T03:41:49ZengNature PortfolioScientific Reports2045-23222025-03-0115111810.1038/s41598-025-94160-5CDX1 improves nicotine induced cardiac fibroblasts activation and cardiomyocyte hypertrophy by alleviating autophagic flux impairment through modulation of LAPTM4BYue-yan Li0Fan-liang Meng1Si-yuan Zhou2Jia-min Du3Wen-jing Li4Qi-yun Liu5Lei Wu6Meng-meng Zhao7Yi Jin8Qun-ye Zhang9Ying Li10Guo-hai Su11Department of Cardiology, Jinan Central Hospital, Shandong UniversityAffiliated Hospital of Shandong University of Traditional Chinese MedicineDepartment of Cardiology, Jinan Central Hospital, Shandong UniversityDepartment of Cardiology, Jinan Central Hospital, Shandong UniversityResearch Center for Translational Medicine, Central Hospital Affiliated to Shandong First Medical UniversityDepartment of Cardiology, Shandong Second Medical UniversityResearch Center for Translational Medicine, Central Hospital Affiliated to Shandong First Medical UniversityResearch Center for Translational Medicine, Central Hospital Affiliated to Shandong First Medical UniversityResearch Center for Translational Medicine, Central Hospital Affiliated to Shandong First Medical UniversityThe Key Laboratory of Cardiovascular Remodeling and Function Research, Department of Cardiology, Qilu Hospital, Shandong UniversityDepartment of Cardiology, Jinan Central Hospital, Shandong UniversityDepartment of Cardiology, Jinan Central Hospital, Shandong UniversityAbstract Nicotine-induced impairment of autophagic flux promotes the onset of myocardial remodelling, thereby exacerbating heart failure. In this study, we investigated the role and molecular mechanisms of the transcription factor CDX1 in cardiac fibroblasts (CFs) activation and cardiomyocyte hypertrophy induced by nicotine. We found that CDX1 expression was increased in response to nicotine. However, a decrease in CDX1 further exacerbated the nicotine-induced blockade of autophagic flux, thereby aggravating CFs activation and cardiomyocyte hypertrophy. This effect was attributed to the suppression of the autophagic regulator LAPTM4B transcription by CDX1 and the subsequent activation of the mTOR pathway. In contrast, CDX1 overexpression promoted LAPTM4B expression, resulting in the opposite effect. In conclusion, our study demonstrated that CDX1/LAPTM4B axis could alleviate nicotine-induced autophagy flux impairment by inhibiting mTORC1 pathway activation, thereby alleviating CFs activation and cardiomyocyte hypertrophy, and exerting cardioprotective functions.https://doi.org/10.1038/s41598-025-94160-5CDX1LAPTM4BAutophagic fluxNicotineCardiomyocyte hypertrophyFibroblast activation |
| spellingShingle | Yue-yan Li Fan-liang Meng Si-yuan Zhou Jia-min Du Wen-jing Li Qi-yun Liu Lei Wu Meng-meng Zhao Yi Jin Qun-ye Zhang Ying Li Guo-hai Su CDX1 improves nicotine induced cardiac fibroblasts activation and cardiomyocyte hypertrophy by alleviating autophagic flux impairment through modulation of LAPTM4B Scientific Reports CDX1 LAPTM4B Autophagic flux Nicotine Cardiomyocyte hypertrophy Fibroblast activation |
| title | CDX1 improves nicotine induced cardiac fibroblasts activation and cardiomyocyte hypertrophy by alleviating autophagic flux impairment through modulation of LAPTM4B |
| title_full | CDX1 improves nicotine induced cardiac fibroblasts activation and cardiomyocyte hypertrophy by alleviating autophagic flux impairment through modulation of LAPTM4B |
| title_fullStr | CDX1 improves nicotine induced cardiac fibroblasts activation and cardiomyocyte hypertrophy by alleviating autophagic flux impairment through modulation of LAPTM4B |
| title_full_unstemmed | CDX1 improves nicotine induced cardiac fibroblasts activation and cardiomyocyte hypertrophy by alleviating autophagic flux impairment through modulation of LAPTM4B |
| title_short | CDX1 improves nicotine induced cardiac fibroblasts activation and cardiomyocyte hypertrophy by alleviating autophagic flux impairment through modulation of LAPTM4B |
| title_sort | cdx1 improves nicotine induced cardiac fibroblasts activation and cardiomyocyte hypertrophy by alleviating autophagic flux impairment through modulation of laptm4b |
| topic | CDX1 LAPTM4B Autophagic flux Nicotine Cardiomyocyte hypertrophy Fibroblast activation |
| url | https://doi.org/10.1038/s41598-025-94160-5 |
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