TGF-β1 promotes SCD1 expression via the PI3K-Akt-mTOR-SREBP1 signaling pathway in lung fibroblasts

Respiratory Research

Research

Changhui Yu¹  Shaoxi Cai¹  Jieyi Liu¹  Shixiu Liang¹  Zili Zhou¹  Jinming Zhang¹  Haijin Zhao¹  Zicong Zhou¹  Fei Zou²  Xiaojing Meng² 

[1] Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China;Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Occupational Health and Medicine, School of Public Health, Southern Medical University, 510515, Guangzhou, China;

关键词: House dust mite;    Airway remodeling;    Fibroblasts;    SCD1;    SREBP1;   

DOI  :  10.1186/s12931-023-02313-9

 received in 2022-04-02, accepted in 2023-01-02,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundLung fibroblast activation is associated with airway remodeling during asthma progression. Stearoyl-CoA desaturase 1 (SCD1) plays an important role in the response of fibroblasts to growth factors. This study aimed to explore the effects of SCD1 on fibroblast activation induced by transforming growth factor-β1 (TGF-β1) and the role of the phosphatidylinositol-3-kinase-AKT serine-threonine protein kinase-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway on the regulation of SCD1 expression in airway remodeling.MethodsFemale C57BL/6 mice were sensitized and challenged with house dust mites to generate a chronic asthma model. The inhibitor of SCD1 was injected i.g. before each challenge. The airway hyper-responsiveness to methacholine was evaluated, and airway remodeling and airway inflammation were assessed by histology. The effects of SCD1 on fibroblast activation were evaluated in vitro using an SCD1 inhibitor and oleic acid and via the knockdown of SCD1. The involvement of the PI3K-Akt-mTOR-sterol regulatory element-binding protein 1 (SREBP1) pathway in lung fibroblasts was investigated using relevant inhibitors.ResultsThe expression of SCD1 was increased in fibroblasts exposed to TGF-β1. The inhibition of SCD1 markedly ameliorated airway remodeling and lung fibroblast activation in peripheral airways. The knockdown or inhibition of SCD1 resulted in significantly reduced extracellular matrix production in TGF-β1-treated fibroblasts, but this effect was reversed by the addition of exogenous oleic acid. The PI3K-Akt-mTOR-SREBP1 pathway was found to be involved in the regulation of SCD1 expression and lung fibroblast activation.ConclusionsThe data obtained in this study indicate that SCD1 expression contributes to fibroblast activation and airway remodeling and that the inhibition of SCD1 may be a therapeutic strategy for airway remodeling in asthma.

【 授权许可】

CC BY   
© The Author(s) 2023

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