RONIN/HCF1‐TFEB Axis Protects Against D‐Galactose‐Induced Cochlear Hair Cell Senescence Through Autophagy Activation
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.
Authors
- Wei Cao (ORCID: https://orcid.org/0000-0002-8546-6090)
- Qiaojun Fang (ORCID: https://orcid.org/0000-0002-2856-3281)
- Lingna Guo
- Renjie Chai (ORCID: https://orcid.org/0000-0002-3885-543X)
- Yuhua Zhang (ORCID: https://orcid.org/0000-0003-0901-935X)
- Yongjie Wei
- Fang Ma (ORCID: https://orcid.org/0009-0008-5339-9349)
- Buwei Shao (ORCID: https://orcid.org/0009-0001-3926-1545)
- Jun S. Song (ORCID: https://orcid.org/0000-0002-0422-2175)
- Zuhong He (ORCID: https://orcid.org/0000-0001-6409-4366)
- Jianming Yang (ORCID: https://orcid.org/0000-0002-2996-399X)
- Su‐Hua Sha (ORCID: https://orcid.org/0000-0002-4425-8586)
- Yun Xiao (ORCID: https://orcid.org/0000-0001-8514-8175)
- Lei Zhang (ORCID: https://orcid.org/0000-0001-7769-7377)
- Nan Cheng
- Jingwen Yang (ORCID: https://orcid.org/0000-0002-8206-2584)
- Yongjun Zhu (ORCID: https://orcid.org/0000-0002-3630-3893)
- Yan Xu (ORCID: https://orcid.org/0009-0001-3964-4343)
- Zheng Ying
Institutions
- Beijing Institute of Technology (CN)
- University of Electronic Science and Technology of China (CN)
- Medical University of South Carolina (US)
- Tel Aviv University (IL)
- Anhui Medical University (CN)
- Nantong University (CN)
- Wuhan University (CN)
- Soochow University (CN)
- Hefei University (CN)
- Zhongda Hospital Southeast University (CN)
- Aerospace Center Hospital (CN)
- Zhongnan Hospital of Wuhan University (CN)
- Second Affiliated Hospital of Anhui Medical University (CN)
- State Key Laboratory of Digital Medical Engineering (CN)
- Southeast University (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-02-22
- DOI
- https://doi.org/10.1002/advs.202407880
- Citations
- 16
- Primary Topic
- Antioxidants, Aging, Portulaca oleracea
- Type
- article
- Field-Weighted Citation Impact
- 14.55
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Jiangsu Province
- Department of Science and Technology of Sichuan Province
- National Key Research and Development Program of China