Deficiency of DEK proto-oncogene alleviates allergic rhinitis by inhibiting RhoA/Ezrin-mediated mitochondrial fission

Longzhu Dai , Yongde Jin , Jingmei Chai , Jianing Yang , Jiangang Wang , Mu Chen , Liangchang Li , Chongyang Wang , Guanghai Yan

Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (11) : 1947 -1959.

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Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (11) :1947 -1959. DOI: 10.1002/ame2.12523
ORIGINAL ARTICLE
Deficiency of DEK proto-oncogene alleviates allergic rhinitis by inhibiting RhoA/Ezrin-mediated mitochondrial fission
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Abstract

Background: Allergic rhinitis (AR) is a kind of immune disease mediated by IgE. We are intrigued by the potential role of DEK proto-oncogene (DEK) in inflammation-related diseases. We investigated the effects and mechanisms of DEK in treating AR, aiming to identify potential new treatment targets for AR.

Methods: The AR mouse model was induced by house dust mite (HDM) (1 mg/mL). HNEpCs stimulated by HDM (1 mg/mL) were pretreated for 24 h with or without DEK lentivirus. The effect of DEK knockout or knockdown on AR was evaluated in vitro and in vivo using western blotting, ELISA, flow cytometry, real-time quantitative PCR, immunohistochemistry, HE staining, PAS staining, Diff staining, and immunofluorescence.

Results: After DEK knockdown, the inflammatory response of AR mice was reduced. In addition, DEK deletion mitigated nasal tissue damage and mitochondrial division. Our further studies showed that DEK deletion or inhibition led to the down-regulation of RhoA activity and decreased phosphorylation of Ezrin and Drp1 proteins, and inhibited mitochondrial division. Overall, DEK deficiency mitigated AR by down-regulating RhoA/Ezrin/Drp1 pathway activity.

Conclusion: DEK alleviates AR through RhoA/Ezrin/Drp1 signaling pathway, which provides a new perspective for developing improved therapies and understanding the pathogenesis of AR.

Keywords

allergic rhinitis / DEK / Ezrin / house dust mite / mitochondria

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Longzhu Dai, Yongde Jin, Jingmei Chai, Jianing Yang, Jiangang Wang, Mu Chen, Liangchang Li, Chongyang Wang, Guanghai Yan. Deficiency of DEK proto-oncogene alleviates allergic rhinitis by inhibiting RhoA/Ezrin-mediated mitochondrial fission. Animal Models and Experimental Medicine, 2025, 8(11): 1947-1959 DOI:10.1002/ame2.12523

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2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.

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