ArticleHistochemistry and cell biology2022
FOXO3/TGF-β signal-dependent ciliogenesis and cell functions during differentiation of temperature-sensitive mouse cochlear precursor hair cells.
Article in Histochemistry and cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 8 citations in OpenAlex.
- Molecular Mechanisms of Aminoglycoside-Induced Ototoxicity in Murine Auditory Cells: Implications for Otoprotective Drug Development.International journal of molecular sciences · 2025Article
- The role of HDAC11 in age-related hearing loss: Mechanisms and therapeutic implications.Open life sciences · 2025Article
- High water temperature raised the requirements of methionine for spotted seabass (Lateolabrax maculatus).Fish physiology and biochemistry · 2024Article
- Role and regulation of FOXO3a: new insights into breast cancer therapy.Frontiers in pharmacology · 2024Review
- A single-cell level comparison of human inner ear organoids with the human cochlea and vestibular organs.Cell reports · 2023Article
- In focus in HCB.Histochemistry and cell biology · 2022Article
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10 authors at 1 institution in 1 country.
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Abstract
The transcription factor FOXO3 is necessary to preserve cochlear hair cells. Growth factors, including TGF-β, closely contribute to cochlear hair cell regeneration. In the present study, to investigate the roles of FOXO3 in the ciliogenesis and cell functions of cochlear hair cells, UB/OC-2 temperature-sensitive mouse cochlear precursor hair cells were treated with TGF-β receptor type 1 inhibitor EW-7197 or EGF receptor inhibitor AG-1478 after transfection with or without siRNA-FOXO3a. GeneChip analysis revealed that treatment with EW-7197 increased Foxo3 genes and decreased genes of Smads. During cell differentiation, treatment with EW-7197 or AG-1478 induced an increase in length of cilia-like structures that were positive for acetylated tubulin and inhibited cell migration. Treatment with EW-7197 also increased cell metabolism measured as mitochondrial basal respiration (oxygen consumption rate). The effects of EW-7197 were stronger than those of AG-1478. Knockdown of FOXO3 prevented the growth of cilia-like structures induced by EW-7197 or AG-1478 and induced cell migration under treatment with EW-7197. No change of the epithelial cell polarity molecule PAR3 was observed with any treatment. Treatment with the antimicrobial agent amikacin prevented the growth of cilia-like structures induced by EW-7197 and induced apoptosis. Pretreatment with the glucocorticoid dexamethasone inhibited the apoptosis induced by amikacin. This in vitro model of mouse cochlear hair cells suggests that FOXO3/TGF-β signaling plays a crucial role in ciliogenesis and cell functions during differentiation of cochlear hair cells. This model is useful for analysis of the mechanisms of hearing loss and to find therapeutic agents to prevent it.
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