Liu Yudong, Li Jingxian, Wu Zhenyu, Wu Shiyu, Yang Xinwei
Department of Pediatrics, Xijing Hospital, the Fourth Military Medical University, No.127 Changle West Road, Xi'an, 710032, China.
Inflammation. 2024 Dec 27. doi: 10.1007/s10753-024-02222-z.
Fibroblast growth factor 21 (FGF21) modulates the inflammatory response in a range of pathological conditions. However, whether FGF21 modulates asthma remains unexplored. This study sought to investigate its function in asthma using an ovalbumin (OVA)-induced mouse model. Levels of FGF21 were observed to be elevated in mice exhibiting asthmatic symptoms. FGF21 knockout (KO) mice exhibited exacerbated asthmatic pathologies, marked by heightened infiltration of inflammatory cells and elevated release of inflammatory cytokine, compared to wild-type (WT) mice with OVA challenge. Adeno-associated virus (AAV)-mediated overexpression of FGF21 significantly reversed asthmatic pathologies in both WT and FGF21 KO mice. Activated NLRP3 inflammasome was observed in WT mice following OVA challenge, and this response was intensified in FGF21 KO mice, manifested by an upregulation of NLRP3, ASC, cleaved Caspase-1, cleaved Gasdermin D (GSDMD), IL-1β, and IL-18. Pharmacological suppression of NLRP3 ameliorated the aggravated asthmatic pathologies observed in FGF21 KO mice after OVA challenge. Overall, the present work underscores the pivotal function of FGF21 in the pathogenesis of asthma and suggests that FGF21 could serve as a potential target for therapeutic interventions.
成纤维细胞生长因子21（FGF21）在一系列病理状况下调节炎症反应。然而，FGF21是否调节哮喘仍未得到探索。本研究试图使用卵清蛋白（OVA）诱导的小鼠模型来研究其在哮喘中的作用。观察到出现哮喘症状的小鼠体内FGF21水平升高。与接受OVA攻击的野生型（WT）小鼠相比，FGF21基因敲除（KO）小鼠表现出加剧的哮喘病理特征，其标志为炎症细胞浸润增加和炎症细胞因子释放增多。腺相关病毒（AAV）介导的FGF21过表达显著逆转了WT和FGF21 KO小鼠的哮喘病理特征。在OVA攻击后的WT小鼠中观察到激活的NLRP3炎性小体，并且这种反应在FGF21 KO小鼠中增强，表现为NLRP3、ASC、裂解的半胱天冬酶-1、裂解的gasdermin D（GSDMD）、白细胞介素-1β和白细胞介素-18上调。对NLRP3的药理学抑制改善了OVA攻击后FGF21 KO小鼠中观察到的加重的哮喘病理特征。总体而言，目前的工作强调了FGF21在哮喘发病机制中的关键作用，并表明FGF21可作为治疗干预的潜在靶点。
