Wu Shun-Yu, Cai Bo-Yu, Cao Zhi-Wen, Wang Tian-Yu, Liang Cai-Quan, Xu En-Hong, Peng Hu, Liu Huan-Hai
Department of Otolaryngology The Second Affiliated Hospital of the Naval Military Medical University (Shanghai Changzheng Hospital) Shanghai China.
Department of Otolaryngology Jinshan Hospital of Fudan University Shanghai China.
World J Otorhinolaryngol Head Neck Surg. 2024 Jun 27;11(1):86-101. doi: 10.1002/wjo2.186. eCollection 2025 Mar.
This study aims to investigate the role of Sirt5 in regulating eosinophil maturation and activation, specifically focusing on primary eosinophils in mice at the genetic level. Additionally, the study aims to elucidate the underlying mechanism of Sirt5 in eosinophilic inflammation metabolism and identify potential drug targets for the treatment of chronic sinusitis. The findings of this study will provide new insights and a solid theoretical basis for the development of novel therapeutic strategies for eosinophilic chronic rhinosinusitis (eCRS).
Our study investigated the role of Sirt5 gene expression in both non-eCRS and eCRS. We examined the correlation between Sirt5 gene expression and disease severity as well as eosinophil infiltration. Additionally, we utilized a mouse model of eCRS to assess the impact of Sirt5 gene deletion on the disease. To further understand the underlying mechanisms, we conducted experiments at the single-cell level using bone marrow-derived eosinophils. We validated our findings through in vitro culture of eosinophils and intervention experiments. Through these experiments, we aimed to elucidate how Sirt5 regulates target proteins and reshapes their related metabolic pathways.
There is a positive correlation between the severity of eCRS and the expression level of Sirt5 in nasal mucosa. Inhibiting Sirt5 expression can effectively alleviate the abnormal activation of eosinophils and the resulting inflammatory response in eCRS-affected nasal mucosa. Sirt5 exerts its influence on eosinophil metabolism by negatively regulating the succinylation level of pkm2, a critical gene in the amino acid biosynthesis pathway.
The severity of eCRS is closely associated with the expression level of Sirt5. Sirt5 plays a negative regulatory role in the succinylation level of Pkm2 in eosinophils, thereby influencing metabolic remodeling and functional activation in eCRS. Investigating Sirt5 and its downstream metabolic pathways could offer valuable insights into the disease's pathogenesis and facilitate the development of targeted therapeutic strategies. This research holds significant implications for clinical practitioners involved in the diagnosis and treatment of patients with eCRS.
本研究旨在探讨Sirt5在调节嗜酸性粒细胞成熟和激活中的作用，特别关注小鼠原代嗜酸性粒细胞在基因水平上的情况。此外，该研究旨在阐明Sirt5在嗜酸性粒细胞炎症代谢中的潜在机制，并确定治疗慢性鼻窦炎的潜在药物靶点。本研究的结果将为嗜酸性粒细胞性慢性鼻-鼻窦炎（eCRS）新治疗策略的开发提供新的见解和坚实的理论基础。
我们的研究调查了Sirt5基因表达在非eCRS和eCRS中的作用。我们检查了Sirt5基因表达与疾病严重程度以及嗜酸性粒细胞浸润之间的相关性。此外，我们利用eCRS小鼠模型评估Sirt5基因缺失对该疾病的影响。为了进一步了解潜在机制，我们使用骨髓来源的嗜酸性粒细胞在单细胞水平上进行实验。我们通过嗜酸性粒细胞的体外培养和干预实验验证了我们的发现。通过这些实验，我们旨在阐明Sirt5如何调节靶蛋白并重塑其相关的代谢途径。
eCRS的严重程度与鼻黏膜中Sirt5的表达水平呈正相关。抑制Sirt5表达可有效减轻eCRS受累鼻黏膜中嗜酸性粒细胞的异常激活及由此产生的炎症反应。Sirt5通过负调节氨基酸生物合成途径中的关键基因pkm2的琥珀酰化水平来影响嗜酸性粒细胞代谢。
eCRS的严重程度与Sirt5的表达水平密切相关。Sirt5在嗜酸性粒细胞中对Pkm2的琥珀酰化水平起负调节作用，从而影响eCRS中的代谢重塑和功能激活。研究Sirt5及其下游代谢途径可为该疾病的发病机制提供有价值的见解，并促进靶向治疗策略的开发。这项研究对参与eCRS患者诊断和治疗的临床医生具有重要意义。
