肺纤维化中细胞因子-细胞因子受体通路的时序性激活

Temporal activation of cytokine-cytokine receptor interaction pathways in pulmonary fibrosis

摘要:

尘肺病属于法定职业病，主要病理特征是肺纤维化，其发病机制涉及复杂的调控过程，然而肺纤维化免疫机制发生与演变的时序规律尚未明晰。本研究旨在系统揭示二氧化硅诱导肺纤维化过程中细胞因子-细胞因子受体相互作用通路的动态变化与机制，通过自然吸入式暴露系统构建小鼠肺纤维化模型，结合病理染色、转录组测序及分子生物学验证等方法进行时序性分析。结果表明，该通路在纤维化全过程呈现持续性激活状态，CXCL1和CXCL2等关键基因的表达呈时序性上调；蛋白层面进一步证实，CXCL2表达在染尘中期达到峰值，而IL-33蛋白水平随纤维化进展持续升高并伴随炎症细胞募集。通过以上结果可以得出结论，细胞因子-细胞因子受体通路的时序性激活是推动肺纤维化进展的核心机制，本研究为针对免疫通路的干预策略提供了重要的理论依据。

Abstract:

As a legally recognized occupational disease characterized by pulmonary fibrosis, silicosis involves complex pathogenic mechanisms. Nevertheless, the temporal sequence of the onset and progression of immune mechanisms underlying pulmonary fibrosis remains to be elucidated. This study aims to systematically elucidate the dynamic changes and underlying mechanisms of the cytokine-cytokine receptor interaction pathway during silicon dioxide-induced pulmonary fibrosis. A mouse model of pulmonary fibrosis was established using a natural inhalation exposure system, and temporal analyses were conducted through histopathological staining, transcriptome sequencing, and molecular biological validation. The results revealed that this pathway was persistently activated throughout the entire fibrotic process. The expression of key genes, such as CXCL1 and CXCL2, was temporally upregulated. Protein-level validation further confirmed that CXCL2 expression peaked at the mid-stage of dust exposure, while IL-33 protein levels progressively increased with the advancement of fibrosis, accompanied by the recruitment of inflammatory cells. The study concludes that the temporal activation of the cytokine-cytokine receptor interaction pathway is a core mechanism driving the progression of pulmonary fibrosis, providing a crucial theoretical basis for developing intervention strategies targeting immune pathways.