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

Q1 Health Professions

Animal models and experimental medicine Pub Date : 2024-12-12 DOI:10.1002/ame2.12523

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

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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.

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DEK原癌基因缺乏通过抑制RhoA/ ezrin介导的线粒体裂变来缓解变应性鼻炎。

背景：变应性鼻炎是一种由IgE介导的免疫性疾病。DEK原癌基因（DEK）在炎症相关疾病中的潜在作用引起了我们的兴趣。我们研究了DEK治疗AR的作用及其机制，旨在寻找可能的治疗AR的新靶点。方法：采用屋尘螨（HDM）（1 mg/mL）诱导AR小鼠模型。用HDM （1 mg/mL）刺激HNEpCs，用DEK慢病毒或不加DEK慢病毒预处理24h。采用western blotting、ELISA、流式细胞术、实时定量PCR、免疫组织化学、HE染色、PAS染色、Diff染色、免疫荧光等方法，在体外和体内评价DEK敲除或敲低对AR的影响。结果：敲除DEK后，AR小鼠的炎症反应明显减轻。此外，DEK缺失减轻了鼻组织损伤和线粒体分裂。我们进一步的研究表明，DEK的缺失或抑制导致RhoA活性下调，Ezrin和Drp1蛋白磷酸化降低，线粒体分裂受到抑制。总的来说，DEK缺乏通过下调RhoA/Ezrin/Drp1通路活性来减轻AR。结论：DEK通过RhoA/Ezrin/Drp1信号通路减轻AR，为开发改进的治疗方法和了解AR的发病机制提供了新的视角。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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