Chloride intracellular channel CLIC3 mediates fibroblast cellular senescence by interacting with ERK7
Abstract Cellular senescence (CS) is recognized as a critical driver of aging and age-related disorders. Recent studies have emphasized the roles of ion channels as key mediators of CS. Nonetheless, the roles and regulatory mechanisms of chloride intracellular channels (CLICs) during CS remain large...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07482-5 |
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| author | Changjiao Luan Yue Gao Jun Zhao Xiaohui Zhang Chaofan Wang Wentao Sun Yucheng Li Xinxing Yang Jiaxiao Chen Weili Liu Weijuan Gong Xingjie Ma |
| author_facet | Changjiao Luan Yue Gao Jun Zhao Xiaohui Zhang Chaofan Wang Wentao Sun Yucheng Li Xinxing Yang Jiaxiao Chen Weili Liu Weijuan Gong Xingjie Ma |
| author_sort | Changjiao Luan |
| collection | DOAJ |
| description | Abstract Cellular senescence (CS) is recognized as a critical driver of aging and age-related disorders. Recent studies have emphasized the roles of ion channels as key mediators of CS. Nonetheless, the roles and regulatory mechanisms of chloride intracellular channels (CLICs) during CS remain largely unexplored. In this study, we conducted RNA sequencing on bleomycin-induced senescent lung tissues from mice and identified Clic3 as the most significantly upregulated CLIC member. Furthermore, our findings revealed that the knockdown of CLIC3 mitigated intracellular chloride ion lose, mitochondrial dysfunction, nuclear enlargement, DNA damage, CS progression, and expression of senescence-associated secretory phenotype (SASP) triggered by bleomycin. Mechanistically, CLIC3 controls CS by translocating to the membrane where it interacts with extracellular signal-regulated kinase 7 (ERK7). Overall, our work demonstrates that the chloride intracellular channel CLIC3 modulates CS by repressing ERK7 activity and provides novel insights into the role of chloride channels. |
| format | Article |
| id | doaj-art-59250a95fb73443d86f308573120dd75 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-59250a95fb73443d86f308573120dd752025-01-19T12:35:37ZengNature PortfolioCommunications Biology2399-36422025-01-018111110.1038/s42003-025-07482-5Chloride intracellular channel CLIC3 mediates fibroblast cellular senescence by interacting with ERK7Changjiao Luan0Yue Gao1Jun Zhao2Xiaohui Zhang3Chaofan Wang4Wentao Sun5Yucheng Li6Xinxing Yang7Jiaxiao Chen8Weili Liu9Weijuan Gong10Xingjie Ma11Laboratory of Intensive Care, Laboratory for Prevention and Translation of Geriatric Diseases, The Affiliated Hospital of Yangzhou UniversityLaboratory of Intensive Care, Laboratory for Prevention and Translation of Geriatric Diseases, The Affiliated Hospital of Yangzhou UniversityDepartment of Lung, The Third People’s Hospital of YangzhouDepartment of Thoracic Surgery, The Affiliated Hospital of Yangzhou UniversityLaboratory of Intensive Care, Laboratory for Prevention and Translation of Geriatric Diseases, The Affiliated Hospital of Yangzhou UniversityLaboratory of Intensive Care, Laboratory for Prevention and Translation of Geriatric Diseases, The Affiliated Hospital of Yangzhou UniversityLaboratory of Intensive Care, Laboratory for Prevention and Translation of Geriatric Diseases, The Affiliated Hospital of Yangzhou UniversityLaboratory of Intensive Care, Laboratory for Prevention and Translation of Geriatric Diseases, The Affiliated Hospital of Yangzhou UniversityLaboratory of Intensive Care, Laboratory for Prevention and Translation of Geriatric Diseases, The Affiliated Hospital of Yangzhou UniversityLaboratory of Intensive Care, Laboratory for Prevention and Translation of Geriatric Diseases, The Affiliated Hospital of Yangzhou UniversityLaboratory of Intensive Care, Laboratory for Prevention and Translation of Geriatric Diseases, The Affiliated Hospital of Yangzhou UniversityLaboratory of Intensive Care, Laboratory for Prevention and Translation of Geriatric Diseases, The Affiliated Hospital of Yangzhou UniversityAbstract Cellular senescence (CS) is recognized as a critical driver of aging and age-related disorders. Recent studies have emphasized the roles of ion channels as key mediators of CS. Nonetheless, the roles and regulatory mechanisms of chloride intracellular channels (CLICs) during CS remain largely unexplored. In this study, we conducted RNA sequencing on bleomycin-induced senescent lung tissues from mice and identified Clic3 as the most significantly upregulated CLIC member. Furthermore, our findings revealed that the knockdown of CLIC3 mitigated intracellular chloride ion lose, mitochondrial dysfunction, nuclear enlargement, DNA damage, CS progression, and expression of senescence-associated secretory phenotype (SASP) triggered by bleomycin. Mechanistically, CLIC3 controls CS by translocating to the membrane where it interacts with extracellular signal-regulated kinase 7 (ERK7). Overall, our work demonstrates that the chloride intracellular channel CLIC3 modulates CS by repressing ERK7 activity and provides novel insights into the role of chloride channels.https://doi.org/10.1038/s42003-025-07482-5 |
| spellingShingle | Changjiao Luan Yue Gao Jun Zhao Xiaohui Zhang Chaofan Wang Wentao Sun Yucheng Li Xinxing Yang Jiaxiao Chen Weili Liu Weijuan Gong Xingjie Ma Chloride intracellular channel CLIC3 mediates fibroblast cellular senescence by interacting with ERK7 Communications Biology |
| title | Chloride intracellular channel CLIC3 mediates fibroblast cellular senescence by interacting with ERK7 |
| title_full | Chloride intracellular channel CLIC3 mediates fibroblast cellular senescence by interacting with ERK7 |
| title_fullStr | Chloride intracellular channel CLIC3 mediates fibroblast cellular senescence by interacting with ERK7 |
| title_full_unstemmed | Chloride intracellular channel CLIC3 mediates fibroblast cellular senescence by interacting with ERK7 |
| title_short | Chloride intracellular channel CLIC3 mediates fibroblast cellular senescence by interacting with ERK7 |
| title_sort | chloride intracellular channel clic3 mediates fibroblast cellular senescence by interacting with erk7 |
| url | https://doi.org/10.1038/s42003-025-07482-5 |
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