Department of Respiratory and Critical Care Medicine, The People's Hospital of China Three Gorges University, The First People's Hospital of Yichang, Yichang, China.
Department of Gastroenterology, The People's Hospital of China Three Gorges University, The First People's Hospital of Yichang, Yichang, China.
Front Immunol. 2023 Apr 14;14:1159856. doi: 10.3389/fimmu.2023.1159856. eCollection 2023.
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease with limited therapeutic options. Recent studies have demonstrated that chemokines play a vital role in IPF pathogenesis. In the present study, we explored whether the gene signature associated with chemokines could be used as a reliable biological marker for patients with IPF.
Chemokine-related differentially expressed genes (CR-DEGs) in IPF and control lung tissue samples were identified using data from the Gene Expression Omnibus database. A chemokine-related signature of the diagnostic model was established using the LASSO-Cox regression. In addition, unsupervised cluster analysis was conducted using consensus-clustering algorithms. The CIBERSORT algorithm was used to calculate immune cell infiltration across patient subgroups. Finally, we established a mouse model of bleomycin-induced pulmonary fibrosis and a model of fibroblasts treated with TGFβ1. Expression levels of chemokine-related signature genes were determined using real-time quantitative polymerase chain reaction (RT-qPCR).
We established a chemokine-related eleven-gene signature of a diagnostic model consisting of CXCL2, CCRL2, ARRB1, XCL1, GRK5, PPBP, CCL19, CCL13, CCL11, CXCL6, and CXCL13, which could easily distinguish between IPF patients and controls. Additionally, we identified two subtypes of IPF samples based on chemokine-related gene expression. Pulmonary function parameters and stromal scores were significantly higher in subtype 1 than in subtype 2. Several immune cell types, especially plasma cells and macrophages, differ significantly between the two subtypes. RT-qPCR results showed that the expression levels of and increased considerably in bleomycin-induced mice. Meanwhile, , , , and expression was significantly reduced. Furthermore, multiple chemokine-related genes were altered in TGFβ1 or TNFα-induced fibroblast cells.
A novel chemokine-related eleven-signature of diagnostic model was developed. These genes are potential biomarkers of IPF and may play essential roles in its pathogenesis.
特发性肺纤维化（IPF）是一种慢性进行性间质性肺疾病，治疗选择有限。最近的研究表明趋化因子在 IPF 的发病机制中起着至关重要的作用。在本研究中，我们探讨了与趋化因子相关的基因特征是否可作为 IPF 患者的可靠生物标志物。
使用基因表达综合数据库中的数据，鉴定 IPF 和对照肺组织样本中的趋化因子相关差异表达基因（CR-DEGs）。使用 LASSO-Cox 回归建立诊断模型的趋化因子相关特征。此外，使用共识聚类算法进行无监督聚类分析。使用 CIBERSORT 算法计算患者亚组的免疫细胞浸润情况。最后，我们建立了博来霉素诱导的肺纤维化小鼠模型和 TGFβ1 处理的成纤维细胞模型。使用实时定量聚合酶链反应（RT-qPCR）测定趋化因子相关特征基因的表达水平。
我们建立了一个由 11 个基因组成的趋化因子相关诊断模型，该模型由 CXCL2、CCRL2、ARRB1、XCL1、GRK5、PPBP、CCL19、CCL13、CCL11、CXCL6 和 CXCL13 组成，可轻松区分 IPF 患者和对照者。此外，我们根据趋化因子相关基因表达鉴定了两种 IPF 样本亚型。1 型的肺功能参数和基质评分明显高于 2 型。两种亚型之间存在明显差异的几种免疫细胞类型，尤其是浆细胞和巨噬细胞。RT-qPCR 结果表明，博来霉素诱导的小鼠中 和 的表达水平显著增加。同时， 、 、 和 的表达显著降低。此外，TGFβ1 或 TNFα诱导的成纤维细胞中多个趋化因子相关基因发生改变。
开发了一种新的趋化因子相关的十一基因诊断模型。这些基因可能是 IPF 的潜在生物标志物，并可能在其发病机制中发挥重要作用。
