The FGF13‐Caveolin‐1 Axis: A Key Player in the Pathogenesis of Doxorubicin‐ and D‐Galactose‐Induced Premature Cardiac Aging
Abstract Delaying senescence of cardiomyocytes has garnered widespread attention as a potential target for preventing cardiovascular diseases (CVDs). FGF13 (Fibroblast growth factor 13) has been implicated in various pathophysiological processes. However, its role in premature myocardial aging and c...
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Wiley
2025-07-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202501055 |
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| author | Enzhao Shen Yuecheng Wu Weijian Ye Sihang Li Junjie Zhu Meifan Jiang Zhicheng Hu Gaoyong Cao Xiaojing Yi Fan Li Zhouhao Tang Xiaokun Li Kwang Youl Lee Litai Jin Xu Wang Weitao Cong |
| author_facet | Enzhao Shen Yuecheng Wu Weijian Ye Sihang Li Junjie Zhu Meifan Jiang Zhicheng Hu Gaoyong Cao Xiaojing Yi Fan Li Zhouhao Tang Xiaokun Li Kwang Youl Lee Litai Jin Xu Wang Weitao Cong |
| author_sort | Enzhao Shen |
| collection | DOAJ |
| description | Abstract Delaying senescence of cardiomyocytes has garnered widespread attention as a potential target for preventing cardiovascular diseases (CVDs). FGF13 (Fibroblast growth factor 13) has been implicated in various pathophysiological processes. However, its role in premature myocardial aging and cardiomyocyte senescence remains unknown. Adeno‐associated virus 9 (AAV9) vectors expressing FGF13 and cardiac‐specific Fgf13 knockout (Fgf13KO) mice are utilized to reveal that FGF13 overexpression and deficiency exacerbated and alleviated Doxorubicin/D‐galactose‐induced myocardial aging characteristics and functional impairment, respectively. Transcriptomics are employed to identify an association between FGF13 and Caveolin‐1 (Cav1). Mechanistic studies indicated that FGF13 regulated the Cav1 promoter activity and expression through the p38/MAPK pathway and nuclear translocation of p65, as well as the binding level of PTRF to Cav1 to mediate cardiomyocyte senescence. Furthermore, Cav1 overexpression in murine hearts reversed the alleviatory effects of FGF13 deficiency on the Doxorubicin/D‐galactose‐induced myocardial aging phenotype and dysfunction. This study has demonstrated that FGF13 regulated the Cav1‐p53‐p21 axis to augment cardiomyocyte senescence and thereby exacerbated cardiac premature aging and suggests that FGF13 knockdown may be a promising approach to combat CVDs in response to aging and chemotoxicity. |
| format | Article |
| id | doaj-art-2a729efd154248a985b22d1432449b4e |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-2a729efd154248a985b22d1432449b4e2025-08-20T02:43:09ZengWileyAdvanced Science2198-38442025-07-011225n/an/a10.1002/advs.202501055The FGF13‐Caveolin‐1 Axis: A Key Player in the Pathogenesis of Doxorubicin‐ and D‐Galactose‐Induced Premature Cardiac AgingEnzhao Shen0Yuecheng Wu1Weijian Ye2Sihang Li3Junjie Zhu4Meifan Jiang5Zhicheng Hu6Gaoyong Cao7Xiaojing Yi8Fan Li9Zhouhao Tang10Xiaokun Li11Kwang Youl Lee12Litai Jin13Xu Wang14Weitao Cong15School of Pharmaceutical Science Wenzhou Medical University Wenzhou 325035 P. R. ChinaSchool of Pharmaceutical Science Wenzhou Medical University Wenzhou 325035 P. R. ChinaDepartment of Pharmacy The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Wenzhou 325027 P. R ChinaSchool of Pharmaceutical Science Wenzhou Medical University Wenzhou 325035 P. R. ChinaSchool of Pharmaceutical Science Wenzhou Medical University Wenzhou 325035 P. R. ChinaSchool of Pharmaceutical Science Wenzhou Medical University Wenzhou 325035 P. R. ChinaSchool of Pharmaceutical Science Wenzhou Medical University Wenzhou 325035 P. R. ChinaSchool of Pharmaceutical Science Wenzhou Medical University Wenzhou 325035 P. R. ChinaSchool of Pharmaceutical Science Wenzhou Medical University Wenzhou 325035 P. R. ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine Vision and Brain Health) School of Pharmaceutical Science Wenzhou Medical University Wenzhou P. R. ChinaSchool of Pharmaceutical Science Wenzhou Medical University Wenzhou 325035 P. R. ChinaSchool of Pharmaceutical Science Wenzhou Medical University Wenzhou 325035 P. R. ChinaCollege of Pharmacy Research Institute of Pharmaceutical Sciences Chonnam National University Gwangju 61186 Republic of KoreaSchool of Pharmaceutical Science Wenzhou Medical University Wenzhou 325035 P. R. ChinaSchool of Pharmaceutical Science Wenzhou Medical University Wenzhou 325035 P. R. ChinaSchool of Pharmaceutical Science Wenzhou Medical University Wenzhou 325035 P. R. ChinaAbstract Delaying senescence of cardiomyocytes has garnered widespread attention as a potential target for preventing cardiovascular diseases (CVDs). FGF13 (Fibroblast growth factor 13) has been implicated in various pathophysiological processes. However, its role in premature myocardial aging and cardiomyocyte senescence remains unknown. Adeno‐associated virus 9 (AAV9) vectors expressing FGF13 and cardiac‐specific Fgf13 knockout (Fgf13KO) mice are utilized to reveal that FGF13 overexpression and deficiency exacerbated and alleviated Doxorubicin/D‐galactose‐induced myocardial aging characteristics and functional impairment, respectively. Transcriptomics are employed to identify an association between FGF13 and Caveolin‐1 (Cav1). Mechanistic studies indicated that FGF13 regulated the Cav1 promoter activity and expression through the p38/MAPK pathway and nuclear translocation of p65, as well as the binding level of PTRF to Cav1 to mediate cardiomyocyte senescence. Furthermore, Cav1 overexpression in murine hearts reversed the alleviatory effects of FGF13 deficiency on the Doxorubicin/D‐galactose‐induced myocardial aging phenotype and dysfunction. This study has demonstrated that FGF13 regulated the Cav1‐p53‐p21 axis to augment cardiomyocyte senescence and thereby exacerbated cardiac premature aging and suggests that FGF13 knockdown may be a promising approach to combat CVDs in response to aging and chemotoxicity.https://doi.org/10.1002/advs.202501055cardiac premature agingcardiomyocyte senescencecaveolin‐1fibroblast growth factor 13p53 signaling |
| spellingShingle | Enzhao Shen Yuecheng Wu Weijian Ye Sihang Li Junjie Zhu Meifan Jiang Zhicheng Hu Gaoyong Cao Xiaojing Yi Fan Li Zhouhao Tang Xiaokun Li Kwang Youl Lee Litai Jin Xu Wang Weitao Cong The FGF13‐Caveolin‐1 Axis: A Key Player in the Pathogenesis of Doxorubicin‐ and D‐Galactose‐Induced Premature Cardiac Aging Advanced Science cardiac premature aging cardiomyocyte senescence caveolin‐1 fibroblast growth factor 13 p53 signaling |
| title | The FGF13‐Caveolin‐1 Axis: A Key Player in the Pathogenesis of Doxorubicin‐ and D‐Galactose‐Induced Premature Cardiac Aging |
| title_full | The FGF13‐Caveolin‐1 Axis: A Key Player in the Pathogenesis of Doxorubicin‐ and D‐Galactose‐Induced Premature Cardiac Aging |
| title_fullStr | The FGF13‐Caveolin‐1 Axis: A Key Player in the Pathogenesis of Doxorubicin‐ and D‐Galactose‐Induced Premature Cardiac Aging |
| title_full_unstemmed | The FGF13‐Caveolin‐1 Axis: A Key Player in the Pathogenesis of Doxorubicin‐ and D‐Galactose‐Induced Premature Cardiac Aging |
| title_short | The FGF13‐Caveolin‐1 Axis: A Key Player in the Pathogenesis of Doxorubicin‐ and D‐Galactose‐Induced Premature Cardiac Aging |
| title_sort | fgf13 caveolin 1 axis a key player in the pathogenesis of doxorubicin and d galactose induced premature cardiac aging |
| topic | cardiac premature aging cardiomyocyte senescence caveolin‐1 fibroblast growth factor 13 p53 signaling |
| url | https://doi.org/10.1002/advs.202501055 |
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