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.
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TGF-β1 通过肺成纤维细胞中的 PI3K-Akt-mTOR-SREBP1 信号通路促进 SCD1 表达
DOI：
10.1186/s12931-023-02313-9
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发表时间：
2023-01-10
影响因子：
5.8
通讯作者：
中科院分区：
文献类型：
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作者：
肺成纤维细胞活化与哮喘进展过程中的气道重塑相关。硬脂酰辅酶A去饱和酶1（SCD 1）在成纤维细胞对生长因子的反应中起重要作用。本研究旨在探讨SCD 1对转化生长因子-β1（TGF-β1）诱导的成纤维细胞活化的影响，以及磷脂酰肌醇-3-激酶-AKT丝氨酸-苏氨酸蛋白激酶-雷帕霉素机制靶点（PI 3 K-Akt-mTOR）通路对SCD 1表达在气道重塑中的调节作用。致敏雌性C57 BL/6小鼠，并用屋尘螨激发以产生慢性哮喘模型。将SCD 1的抑制剂i.g.每次挑战前评价气道对乙酰甲胆碱的高反应性，并通过组织学评估气道重塑和气道炎症。在体外使用SCD 1抑制剂和油酸并通过敲低SCD 1来评估SCD 1对成纤维细胞活化的影响。使用相关抑制剂研究肺成纤维细胞中PI 3 K-Akt-mTOR-固醇调节元件结合蛋白1（SREBP 1）途径的参与。TGF-β1诱导成纤维细胞SCD 1表达增加。抑制SCD 1可显著改善气道重塑和外周气道肺成纤维细胞活化。在TGF-β1处理的成纤维细胞中，敲低或抑制SCD 1导致细胞外基质产生显著减少，但这种作用可通过添加外源性油酸逆转。PI 3 K-Akt-mTOR-SREBP 1通路参与了SCD 1表达和肺成纤维细胞活化的调节。本研究中获得的数据表明，SCD 1的表达有助于成纤维细胞活化和气道重塑，并且SCD 1的抑制可能是哮喘气道重塑的治疗策略。在线版本包含补充材料，可通过10.1186/s12931-023-02313-9获得。
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s12931-023-02313-9.
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