Fisetin reduces ovalbumin-triggered airway remodeling by preventing phenotypic switching of airway smooth muscle cells.

IF 5.8 2区 医学 Q1 Medicine
Yuanyuan Liu, Qiling Yin, Bin Liu, Zheng Lu, Meijun Liu, Ling Meng, Chao He, Jin Chang
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引用次数: 0

Abstract

Background: The transformation of airway smooth muscle cells (ASMCs) from a quiescent phenotype to a hypersecretory and hypercontractile phenotype is a defining feature of asthmatic airway remodeling. Fisetin, a flavonoid compound, possesses anti-inflammatory characteristics in asthma; yet, its impact on airway remodeling and ASMCs phenotype transition has not been investigated.

Objectives: This research seeked to assess the impact of fisetin on ovalbumin (OVA) induced asthmatic airway remodeling and ASMCs phenotype transition, and clarify the mechanisms through network pharmacology predictions as well as in vivo and in vitro validation.

Methods: First, a fisetin-asthma-ASMCs network was constructed to identify potential targets. Subsequently, cellular and animal studies were carried out to examine the inhibitory effects of fisetin on airway remodeling in asthmatic mice, and to detemine how fisetin impacts the phenotypic transition of ASMCs.

Results: Network analysis indicated that fisetin might affect asthma via mediating the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT) pathway. Intraperitoneal administration of fisetin in vivo reduced airway inflammation and remodeling, as shown by reduced inflammatory cells, decreased T helper type 2 (Th2) cytokine release, diminished collagen accumulation, mitigated airway smooth muscle thickening, and decreased expression of osteopontin (OPN), collagen-I and α-smooth muscle actin (α-SMA). Moreover, fisetin suppressed the PI3K/AKT pathway in asthmatic lung tissue. According to the in vitro data, fisetin downregulated the expression of the synthetic phenotypic proteins OPN and collagen-I, contractile protein α-SMA, and inhibited cellular migration, potentially through the PI3K/AKT pathway.

Conclusion: These results suggest that fisetin inhibits airway remodeling in asthma by regulating ASMCs phenotypic shift, emphasizing that fisetin is a promising candidate for the treatment of airway smooth muscle remodeling.

鱼腥草素能防止气道平滑肌细胞的表型转换,从而减少卵清蛋白引发的气道重塑。
背景:气道平滑肌细胞(ASMC)从静止表型转变为高分泌和高收缩表型是哮喘气道重塑的一个决定性特征。黄酮类化合物鱼腥草素在哮喘中具有抗炎特性,但其对气道重塑和 ASMC 表型转变的影响尚未得到研究:本研究旨在评估鱼腥草素对卵清蛋白(OVA)诱导的哮喘气道重塑和ASMCs表型转换的影响,并通过网络药理学预测以及体内、体外验证阐明其机制:方法:首先,构建了鱼腥草素-哮喘-ASMCs网络,以确定潜在靶点。方法:首先构建了鱼腥草素-哮喘-ASMCs网络,确定潜在靶点,然后进行细胞和动物实验,研究鱼腥草素对哮喘小鼠气道重塑的抑制作用,并确定鱼腥草素如何影响ASMCs的表型转变:结果:网络分析表明,鱼腥草素可能通过介导磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)通路影响哮喘。腹腔注射菲赛汀可减少气道炎症和重塑,具体表现为炎症细胞减少、T辅助2型细胞因子(Th2)释放减少、胶原堆积减少、气道平滑肌增厚减轻,以及骨生成素(OPN)、胶原蛋白-I和α-平滑肌肌动蛋白(α-SMA)表达减少。此外,鱼腥草素还能抑制哮喘肺组织中的 PI3K/AKT 通路。根据体外数据,鱼腥草素可能通过 PI3K/AKT 通路下调了合成表型蛋白 OPN 和胶原蛋白-I、收缩蛋白 α-SMA 的表达,并抑制了细胞迁移:这些结果表明,鱼腥草素通过调节 ASMCs 表型转变抑制了哮喘的气道重塑,强调了鱼腥草素是治疗气道平滑肌重塑的一种有前途的候选药物。
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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来源期刊
Respiratory Research
Respiratory Research RESPIRATORY SYSTEM-
CiteScore
9.70
自引率
1.70%
发文量
314
审稿时长
4-8 weeks
期刊介绍: Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.
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