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TMEM59 ablation leads to loss of olfactory sensory neurons and impairs olfactory functions via interaction with inflammation.
Ma, Zhenjie; Li, Weihao; Zhuang, Liujing; Wen, Tieqiao; Wang, Ping; Yu, Hongmeng; Liu, Yongliang; Yu, Yiqun.
Afiliación
  • Ma Z; School of Life Sciences, Shanghai University, Shanghai, People's Republic of China.
  • Li W; Department of Otolaryngology, Eye, Ear, Nose & Throat Hospital, Fudan University, Shanghai, People's Republic of China; Ear, Nose & Throat Institute, Eye, Ear, Nose & Throat Hospital, Fudan University, Shanghai, People's Republic of China; Clinical and Research Center for Olfactory Disor
  • Zhuang L; Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China; The MOE Frontier Science Center for Brain Science & Brain-machine Integration, Zhejiang University, Hangzhou
  • Wen T; School of Life Sciences, Shanghai University, Shanghai, People's Republic of China.
  • Wang P; Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China; The MOE Frontier Science Center for Brain Science & Brain-machine Integration, Zhejiang University, Hangzhou
  • Yu H; Department of Otolaryngology, Eye, Ear, Nose & Throat Hospital, Fudan University, Shanghai, People's Republic of China; Ear, Nose & Throat Institute, Eye, Ear, Nose & Throat Hospital, Fudan University, Shanghai, People's Republic of China; Clinical and Research Center for Olfactory Disor
  • Liu Y; Department of Otolaryngology, Zibo Central Hospital, Zibo 255036, China. Electronic address: liu_yl@sina.cn.
  • Yu Y; Department of Otolaryngology, Eye, Ear, Nose & Throat Hospital, Fudan University, Shanghai, People's Republic of China; Ear, Nose & Throat Institute, Eye, Ear, Nose & Throat Hospital, Fudan University, Shanghai, People's Republic of China; Clinical and Research Center for Olfactory Disor
Brain Behav Immun ; 111: 151-168, 2023 07.
Article en En | MEDLINE | ID: mdl-37061103
The olfactory epithelium undergoes constant neurogenesis throughout life in mammals. Several factors including key signaling pathways and inflammatory microenvironment regulate the maintenance and regeneration of the olfactory epithelium. In this study, we identify TMEM59 (also known as DCF1) as a critical regulator to the epithelial maintenance and regeneration. Single-cell RNA-Seq data show downregulation of TMEM59 in multiple epithelial cell lineages with aging. Ablation of TMEM59 leads to apparent alteration at the transcriptional level, including genes associated with olfactory transduction and inflammatory/immune response. These differentially expressed genes are key components belonging to several signaling pathways, such as NF-κB, chemokine, etc. TMEM59 deletion impairs olfactory functions, attenuates proliferation, causes loss of both mature and immature olfactory sensory neurons, and promotes infiltration of inflammatory cells, macrophages, microglia cells and neutrophils into the olfactory epithelium and lamina propria. TMEM59 deletion deteriorates regeneration of the olfactory epithelium after injury, with significant reduction in the number of proliferative cells, immature and mature sensory neurons, accompanied by the increasing number of inflammatory cells and macrophages. Anti-inflammation by dexamethasone recovers neuronal generation and olfactory functions in the TMEM59-KO animals, suggesting the correlation between TMEM59 and inflammation in regulating the epithelial maintenance. Collectively, TMEM59 regulates olfactory functions, as well as neuronal generation in the olfactory epithelium via interaction with inflammation, suggesting a potential role in therapy against olfactory dysfunction associated with inflamm-aging.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neuronas Receptoras Olfatorias Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2023 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neuronas Receptoras Olfatorias Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2023 Tipo del documento: Article Pais de publicación: Países Bajos