鞘氨醇-1-磷酸信号通路调控哮喘气道重塑的多靶点作用机制

杨智鹏; 先容; 郗域江; 张晓丽; 欧阳丽; 肖泓

doi:10.16766/j.cnki.issn.1674-4152.004343

鞘氨醇-1-磷酸信号通路调控哮喘气道重塑的多靶点作用机制

doi: 10.16766/j.cnki.issn.1674-4152.004343

1.
云南中医药大学第一临床医学院，云南昆明 650000
2.
云南中医药大学第二临床医学院，云南昆明 650000

基金项目:

云南省“万人计划”名医专项人才项目 YNWR-MY-2019-044

云南省教育厅科学研究基金项目 2025Y0636

云南省第六批中医药师带徒工作项目云卫中医发展发〔2025〕1号

详细信息

通讯作者:
肖泓，E-mail:xiaohong0575@163.com

中图分类号: R562.25
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- 文章访问数: 10
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- PDF下载量: 1
- 被引次数: 0
出版历程
- 收稿日期: 2025-04-03
- 网络出版日期: 2026-04-01

Multi-target mechanisms of the sphingosine-1-phosphate signaling pathway in regulating airway remodeling in asthma

1.
The First Clinical Medical College of Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan 650000, China

摘要

摘要: 鞘氨醇-1-磷酸(S1P)信号通路是鞘脂代谢的核心环节，通过其5种G蛋白偶联受体(S1PR1-5)介导细胞增殖、迁移、存活、免疫细胞趋化和血管生成等多种生物学过程，在免疫调节、炎症反应和组织重塑中扮演关键角色。近年来，随着代谢组学及信号通路研究的深入，S1P信号通路与哮喘等慢性炎症性疾病的关联日益受到关注。哮喘的核心病理特征之一是气道重塑(AR)，表现为气道平滑肌细胞(ASMC)异常增殖与迁移、上皮-间充质转化(EMT)、纤维化病变及病理性血管新生等不可逆结构性改变。目前研究表明，S1P信号通路在AR中发挥多靶点调控作用：其一方面通过激活S1PR2/3-Rho/ROCK及STAT3/YAP/Notch3等信号轴驱动ASMC增殖、迁移与收缩；另一方面协同转化生长因子-β(TGF-β)下调上皮标志物、上调间充质标志物，促进EMT及纤维化进程；同时，与血管内皮生长因子(VEGF)形成协同效应，介导病理性血管新生，加剧缺氧-炎症-重塑的恶性循环。本文系统阐述S1P信号通路在哮喘气道重塑中的多维调控网络及其作为治疗靶点的潜力，旨在为开发靶向干预气道重塑的多靶点治疗新策略提供理论依据。
- 哮喘 /
- 鞘氨醇-1-磷酸 /
- 气道重塑 /
- 信号通路
Abstract: The sphingosine-1-phosphate (S1P) signaling pathway is the key component of sphingolipid metabolism. It mediates cell proliferation, migration, survival, immune cell trafficking, and angiogenesis via S1PR1-5 receptors. It plays key roles in immunomodulation, inflammation, and tissue remodeling. Recent advances in metabolomics and signaling research highlight the growing link between S1P signaling and chronic inflammatory diseases like such as asthma. A core pathological feature of asthma is airway remodeling (AR), characterized by irreversible structural alterations including abnormal airway smooth muscle cell (ASMC) proliferation or migration, epithelial-mesenchymal transition (EMT), fibrosis, and pathological angiogenesis. Current research shows the S1P pathway targets multiple aspects of asthma AR: it drives ASMC proliferation, migration, and contraction by activating axes such as S1PR2/3-Rho/ROCK and STAT3/YAP/Notch3; it downregulates epithelial markers while upregulating mesenchymal markers to promote EMT and fibrosis; and it synergizes with VEGF to mediate pathological angiogenesis, exacerbating the hypoxia-inflammation-remodeling cycle. This review systematically examines the regulatory network of the S1P pathway in asthma AR and its therapeutic potential, aiming to provide a foundation for novel, multi-targeted strategies for AR intervention.
- Asthma /
- Sphingosine-1-phosphate /
- Airway remodeling /
- Signaling pathway

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