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麻黄汤通过抑制 SP1/FGFR3/PI3K/AKT 轴减轻哮喘气道炎症和重塑。

Mahuang Decoction Attenuates Airway Inflammation and Remodeling in Asthma via Suppression of the SP1/FGFR3/PI3K/AKT Axis.

机构信息

Children's Medical Center, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130021, People's Republic of China.

Department of Pediatrics, Beijing Daxing District Maternal and Child Health Care Hospital, Beijing, 102600, People's Republic of China.

出版信息

Drug Des Devel Ther. 2022 Aug 26;16:2833-2850. doi: 10.2147/DDDT.S351264. eCollection 2022.

Abstract

BACKGROUND/PURPOSE: Mahuang decoction (MHD) is a classic famous traditional Chinese medicine and has various pharmacological effects, including anti-inflammation and anti-asthma. In this study, we aimed to investigate the potential protective effect of MHD against asthma and elucidated the underlying mechanism.

MATERIALS AND METHODS

A mouse model of asthma was induced by ovalbumin (OVA) treatment, and then treated with MHD to evaluate its effect on the asthma. Gain- or loss-of-function approaches were performed in SP1 and FGFR3 to study their roles in asthma via measurement of airway inflammation, airway remodeling and airway smooth muscle cell (ASMC) proliferation-related factors.

RESULTS

MHD reduced airway inflammation and remodeling. Additionally, MHD contributed to diminished expression of SP1, which was shown to repress airway inflammation and remodeling. Furthermore, SP1 bound to the FGFR3 promoter, resulting in the FGFR3 transcription promotion and ASMC proliferation. Conversely, FGFR3 knockdown abolished airway inflammation and remodeling, the mechanism of which was related to suppression of the PI3K/AKT signaling pathway. Meanwhile, MHD hindered airway inflammation and remodeling following asthma by suppressing the SP1/FGFR3/PI3K/AKT axis.

CONCLUSION

Taken together, MHD may retard airway inflammation and remodeling by suppressing the SP1/FGFR3/PI3K/AKT axis, which contributes to an extensive understanding of asthma and may provide novel therapeutic options for this disease.

摘要

背景/目的:麻黄汤(MHD)是一种经典的著名中药,具有多种药理作用,包括抗炎和抗哮喘。在这项研究中,我们旨在研究 MHD 对哮喘的潜在保护作用,并阐明其潜在机制。

材料和方法

通过卵清蛋白(OVA)处理诱导哮喘小鼠模型,然后用 MHD 治疗以评估其对哮喘的作用。通过测量气道炎症、气道重塑和气道平滑肌细胞(ASMC)增殖相关因子,采用 SP1 和 FGFR3 的增益或缺失功能方法研究它们在哮喘中的作用。

结果

MHD 减轻气道炎症和重塑。此外,MHD 有助于降低 SP1 的表达,这表明 SP1 抑制气道炎症和重塑。此外,SP1 与 FGFR3 启动子结合,导致 FGFR3 转录促进和 ASMC 增殖。相反,FGFR3 敲低消除了气道炎症和重塑,其机制与抑制 PI3K/AKT 信号通路有关。同时,MHD 通过抑制 SP1/FGFR3/PI3K/AKT 轴来抑制气道炎症和重塑。

结论

总之,MHD 可能通过抑制 SP1/FGFR3/PI3K/AKT 轴来减缓气道炎症和重塑,这有助于更广泛地了解哮喘,并为该疾病提供新的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b009/9427210/6c2ec862d36f/DDDT-16-2833-g0001.jpg

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