2. Academic Validation
  3. SIRT3 knockout aggravates LPS-induced eustachian tube dysfunction

SIRT3 knockout aggravates LPS-induced eustachian tube dysfunction

  • J Otol. 2025 Nov 13;20(4):211-218. doi: 10.26599/JOTO.2025.9540033.
Shimin Zong 1 2 3,  Huimin Zhang 1 2 3,  Ting Li 1 2 3,  Xi Lian 1 2 3,  Wei Tang 1 2 3,  Tianyi Liu 4,  Wenting Yu 1 2 3,  Xuan Yu 1 2 3,  Hongjun Xiao 1 2 3
Affiliations

Affiliations

  • 1 Department of Otorhinolaryngology-Head and Neck Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  • 2 Institute of Otorhinolaryngology-Head and Neck Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  • 3 Hubei Province Clinical Research Center for Deafness and Vertigo,Wuhan 430022, China.
  • 4 Department of Otorhinolaryngology-Head and Neck Surgery, Renmin Hospital, Wuhan University, Wuhan 430060, China.
PMID: 41311539 DOI: 10.26599/JOTO.2025.9540033
Abstract

Purpose: Acute otitis media caused by gram-negative bacteria is a common otological condition among pediatric patients. Eustachian tube dysfunction (ETD) plays a pivotal role in the delayed resolution of acute otitis media, whereas the precise contribution of SIRT3 in this mechanism remains uncertain. This study aims to reveal the involvement of SIRT3 in murine ETD induced by LPS.

Results: Histological analysis showed no baseline differences in ET structure between WT and SIRT3 knockout (SIRT3-KO) mice. However, LPS exposure led to increased goblet cell proliferation and MUC5AC mucus secretion in both genotypes, with SIRT3-KO exacerbating these effects. The SIRT3-KO group displayed reduced cilia length. Functionally, SIRT3-KO mice showed a significantly higher initial POP and decreased MCC compared to the WT group after LPS exposure. Additionally, the active clearance of negative pressure (ACNP) was significantly reduced in SIRT3-KO mice, indicating compromised ET function.

Conclusions: SIRT3-KO increased resistance to ET opening in mice exposed to LPS, and this effect may be related to the upregulated MUC5AC expression, the increased surface tension of the luminal fluid and the impaired MCC function in mice exposed to LPS.

Keywords

LPS; MUC5AC; Sirt3; eustachian tube dysfunction.

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