2. Academic Validation
  3. TGF-β1 promotes SCD1 expression via the PI3K-Akt-mTOR-SREBP1 signaling pathway in lung fibroblasts

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

  • Respir Res. 2023 Jan 10;24(1):8. doi: 10.1186/s12931-023-02313-9.
Zili Zhou 1,  Shixiu Liang 1,  Zicong Zhou 1,  Jieyi Liu 1,  Jinming Zhang 1,  Xiaojing Meng 2,  Fei Zou 2,  Haijin Zhao 1,  Changhui Yu # 1,  Shaoxi Cai # 3
Affiliations

Affiliations

  • 1 Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
  • 2 Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Occupational Health and Medicine, School of Public Health, Southern Medical University, Guangzhou, 510515, China.
  • 3 Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. hxkc@smu.edu.cn.
  • # Contributed equally.
PMID: 36627645 DOI: 10.1186/s12931-023-02313-9
Abstract

Background: Lung 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.

Methods: Female 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.

Results: The 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.

Conclusions: The 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.

Keywords

Airway remodeling; Fibroblasts; House dust mite; SCD1; SREBP1.

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