RONIN/HCF1‐TFEB Axis Protects Against D‐Galactose‐Induced Cochlear Hair Cell Senescence Through Autophagy Activation
Abstract Age‐related hearing loss is characterized by senescent inner ear hair cells (HCs) and reduced autophagy. Despite the improved understanding of these processes, detailed molecular mechanisms underlying cochlear HC senescence remain unclear. Transcription Factor EB (TFEB), a key regulator of...
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Wiley
2025-08-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202407880 |
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| author | Yongjie Wei Yuhua Zhang Wei Cao Nan Cheng Yun Xiao Yongjun Zhu Yan Xu Lei Zhang Lingna Guo Jun Song Su‐hua Sha Buwei Shao Fang Ma Jingwen Yang Zheng Ying Zuhong He Renjie Chai Qiaojun Fang Jianming Yang |
| author_facet | Yongjie Wei Yuhua Zhang Wei Cao Nan Cheng Yun Xiao Yongjun Zhu Yan Xu Lei Zhang Lingna Guo Jun Song Su‐hua Sha Buwei Shao Fang Ma Jingwen Yang Zheng Ying Zuhong He Renjie Chai Qiaojun Fang Jianming Yang |
| author_sort | Yongjie Wei |
| collection | DOAJ |
| description | Abstract Age‐related hearing loss is characterized by senescent inner ear hair cells (HCs) and reduced autophagy. Despite the improved understanding of these processes, detailed molecular mechanisms underlying cochlear HC senescence remain unclear. Transcription Factor EB (TFEB), a key regulator of genes associated with autophagy and lysosomes, crucially affects aging‐related illnesses. However, intricate regulatory networks that influence TFEB activity remain to be thoroughly elucidated. The findings revealed that RONIN (THAP11), through its interaction with host cell factor C1 (HCF1/HCFC1), modulated the transcriptional activity of Tfeb, thus contributing to the mitigation (D‐galatactose [D‐gal]) senescent HC loss. Specifically, RONIN overexpression improved autophagy levels and lysosomal activity and attenuated changes associated with the senescence of HCs triggered by D‐gal. These findings highlight the possibility of using RONIN as a viable therapeutic target to ameliorate presbycusis by enhancing the TFEB function. |
| format | Article |
| id | doaj-art-dee7c768e3904644bb6c48c15c110761 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-dee7c768e3904644bb6c48c15c1107612025-08-20T02:57:53ZengWileyAdvanced Science2198-38442025-08-011229n/an/a10.1002/advs.202407880RONIN/HCF1‐TFEB Axis Protects Against D‐Galactose‐Induced Cochlear Hair Cell Senescence Through Autophagy ActivationYongjie Wei0Yuhua Zhang1Wei Cao2Nan Cheng3Yun Xiao4Yongjun Zhu5Yan Xu6Lei Zhang7Lingna Guo8Jun Song9Su‐hua Sha10Buwei Shao11Fang Ma12Jingwen Yang13Zheng Ying14Zuhong He15Renjie Chai16Qiaojun Fang17Jianming Yang18Department of Otolaryngology‐Head and Neck Surgery The Second Affiliated Hospital of Anhui Medical University Hefei 230601 ChinaDepartment of Otolaryngology‐Head and Neck Surgery The Second Affiliated Hospital of Anhui Medical University Hefei 230601 ChinaDepartment of Otolaryngology‐Head and Neck Surgery The Second Affiliated Hospital of Anhui Medical University Hefei 230601 ChinaDepartment of Otolaryngology‐Head and Neck Surgery The Second Affiliated Hospital of Anhui Medical University Hefei 230601 ChinaDepartment of Otolaryngology‐Head and Neck Surgery The Second Affiliated Hospital of Anhui Medical University Hefei 230601 ChinaDepartment of Otolaryngology‐Head and Neck Surgery The Second Affiliated Hospital of Anhui Medical University Hefei 230601 ChinaDepartment of Otolaryngology‐Head and Neck Surgery The Second Affiliated Hospital of Anhui Medical University Hefei 230601 ChinaDepartment of Otolaryngology‐Head and Neck Surgery The Second Affiliated Hospital of Anhui Medical University Hefei 230601 ChinaDepartment of Otolaryngology‐Head and Neck Surgery The Second Affiliated Hospital of Anhui Medical University Hefei 230601 ChinaDepartment of Otolaryngology‐Head and Neck Surgery The Second Affiliated Hospital of Anhui Medical University Hefei 230601 ChinaDepartment of Pathology and Laboratory Medicine The Medical University of South Carolina Charleston SC 29425 USASchool of Medicine Faculty of Medical & Health Sciences Tel Aviv University Tel Aviv 6997801 IsraelCenter for Scientific Research of Anhui Medical University Hefei 230032 ChinaInternational Department of Hefei 168 High School Hefei 230601 ChinaJiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Soochow University Suzhou 215123 ChinaDepartment of Otorhinolaryngology‐Head and Neck Surgery Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaState Key Laboratory of Digital Medical Engineering Department of Otolaryngology Head and Neck Surgery Zhongda Hospital School of Life Sciences and Technology School of Medicine Advanced Institute for Life and Health Jiangsu Province High‐Tech Key Laboratory for Bio‐Medical Research Southeast University Nanjing 210096 ChinaDepartment of Otolaryngology‐Head and Neck Surgery The Second Affiliated Hospital of Anhui Medical University Hefei 230601 ChinaDepartment of Otolaryngology‐Head and Neck Surgery The Second Affiliated Hospital of Anhui Medical University Hefei 230601 ChinaAbstract Age‐related hearing loss is characterized by senescent inner ear hair cells (HCs) and reduced autophagy. Despite the improved understanding of these processes, detailed molecular mechanisms underlying cochlear HC senescence remain unclear. Transcription Factor EB (TFEB), a key regulator of genes associated with autophagy and lysosomes, crucially affects aging‐related illnesses. However, intricate regulatory networks that influence TFEB activity remain to be thoroughly elucidated. The findings revealed that RONIN (THAP11), through its interaction with host cell factor C1 (HCF1/HCFC1), modulated the transcriptional activity of Tfeb, thus contributing to the mitigation (D‐galatactose [D‐gal]) senescent HC loss. Specifically, RONIN overexpression improved autophagy levels and lysosomal activity and attenuated changes associated with the senescence of HCs triggered by D‐gal. These findings highlight the possibility of using RONIN as a viable therapeutic target to ameliorate presbycusis by enhancing the TFEB function.https://doi.org/10.1002/advs.202407880aging‐related hearing lossautophagyhair cellRONIN/THAP11Tfeb |
| spellingShingle | Yongjie Wei Yuhua Zhang Wei Cao Nan Cheng Yun Xiao Yongjun Zhu Yan Xu Lei Zhang Lingna Guo Jun Song Su‐hua Sha Buwei Shao Fang Ma Jingwen Yang Zheng Ying Zuhong He Renjie Chai Qiaojun Fang Jianming Yang RONIN/HCF1‐TFEB Axis Protects Against D‐Galactose‐Induced Cochlear Hair Cell Senescence Through Autophagy Activation Advanced Science aging‐related hearing loss autophagy hair cell RONIN/THAP11 Tfeb |
| title | RONIN/HCF1‐TFEB Axis Protects Against D‐Galactose‐Induced Cochlear Hair Cell Senescence Through Autophagy Activation |
| title_full | RONIN/HCF1‐TFEB Axis Protects Against D‐Galactose‐Induced Cochlear Hair Cell Senescence Through Autophagy Activation |
| title_fullStr | RONIN/HCF1‐TFEB Axis Protects Against D‐Galactose‐Induced Cochlear Hair Cell Senescence Through Autophagy Activation |
| title_full_unstemmed | RONIN/HCF1‐TFEB Axis Protects Against D‐Galactose‐Induced Cochlear Hair Cell Senescence Through Autophagy Activation |
| title_short | RONIN/HCF1‐TFEB Axis Protects Against D‐Galactose‐Induced Cochlear Hair Cell Senescence Through Autophagy Activation |
| title_sort | ronin hcf1 tfeb axis protects against d galactose induced cochlear hair cell senescence through autophagy activation |
| topic | aging‐related hearing loss autophagy hair cell RONIN/THAP11 Tfeb |
| url | https://doi.org/10.1002/advs.202407880 |
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