Evidence map›Paper›PMID 41995135›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Restoring Iron Homeostasis via Smoothened Inhibition: A Novel Strategy Against Hearing Loss.

Huanyu Mao, Xiang Li, Yaqi Liao, Liman Liu, Xian Gao, Hailiang Lin, Wenli Ni, Huawei Li, Yan Chen, Wenyan Li

Abstract read
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In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Huanyu MaoENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center For Brain Science, Institutes of Biomedical Sciences, Fudan University, Shanghai, P. R. China.
Xiang LiENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center For Brain Science, Institutes of Biomedical Sciences, Fudan University, Shanghai, P. R. China.
Yaqi LiaoENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center For Brain Science, Institutes of Biomedical Sciences, Fudan University, Shanghai, P. R. China.
Liman LiuDepartment of Surgery-Otolaryngology, Yale University Medical School, New Haven, Connecticut, USA.
Xian GaoENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center For Brain Science, Institutes of Biomedical Sciences, Fudan University, Shanghai, P. R. China.
Hailiang LinENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center For Brain Science, Institutes of Biomedical Sciences, Fudan University, Shanghai, P. R. China.
Wenli NiENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center For Brain Science, Institutes of Biomedical Sciences, Fudan University, Shanghai, P. R. China.
Huawei LiENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center For Brain Science, Institutes of Biomedical Sciences, Fudan University, Shanghai, P. R. China.
Yan ChenENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center For Brain Science, Institutes of Biomedical Sciences, Fudan University, Shanghai, P. R. China.
Wenyan LiENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center For Brain Science, Institutes of Biomedical Sciences, Fudan University, Shanghai, P. R. China.ORCID https://orcid.org/0000-0001-9575-7812

Funding

Key Research and Development Program of Zhejiang Province 2024C03238National Key R&D Program of China 2025YFC3508205National Natural Science Foundation of China 82192861National Natural Science Foundation of China 82271159National Natural Science Foundation of China 82271170National Natural Science Foundation of China 82425018the STI2030-Major Projects 2022ZD0205400
6 · The paper itself

Abstract

Sensorineural hearing loss (SNHL) induced by noise or aminoglycoside antibiotics is a significant public health concern without any FDA-approved pharmaceutical therapies. Dysregulation of iron homeostasis and its subsequently induced ferroptosis has increasingly been identified as a key mechanism underlying cochlear hair cell (HC) damage. Nevertheless, the therapeutic targets for restoring iron balance for hearing protection remain poorly investigated. In this study, we uncover a previously unrecognized role of the SMO pathway in regulating iron homeostasis. SMO expression was rapidly upregulated and activated in HCs following injury. Both genetic ablation of Smo and pharmacological inhibition of SMO reduced iron accumulation and lipid peroxidation, promoting HC survival and preserving auditory function in mouse models of ototoxic- and noise-induced hearing loss. Mechanistically, SMO inhibition suppressed ATF2 phosphorylation, resulting in downregulation of IRP1, which decreased iron accumulation via downregulation of Tfrc and upregulation of Fpn, ultimately protecting HCs from ferroptosis. Notably, treatment with the SMO inhibitor SANT-1 nearly restored auditory thresholds to baseline levels in mice subjected to ototoxic injury. Our findings identify the SMO-ATF2-IRP1-FPN/TFRC axis as a central regulator of cochlear iron homeostasis and propose SMO inhibition as a promising therapeutic strategy for SNHL through precise modulation of iron metabolism.

Indexed as

Hearing LossHearing Loss, SensorineuralHomeostasisIronSmoothened ReceptorAnimalsDisease Models, AnimalFerroptosisHair Cells, AuditoryMaleMiceSignal TransductionIronSmoothened ReceptorSmo protein, mouseferroptosishair cells preservationhearing losshedgehog signalingiron homeostasissmoothened

Identifiers

PMID41995135
PMCPMC13205593

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.