Respiratory Research Unit, Health Research Institute-Fundación Jimenez Diaz University Hospital, Madrid, Spain.
Molecular Genetics Department, Ramón y Cajal University Hospital-IRYCIS, Madrid, Spain.
PLoS One. 2024 Aug 22;19(8):e0309166. doi: 10.1371/journal.pone.0309166. eCollection 2024.
Chronic obstructive pulmonary disease is a common chronic lung disease with an ever-increasing incidence. Despite years of drug research and approvals, we are still not able to halt progress or restore normal lung function. Our previous studies have demonstrated that liver growth factor-LGF has an effect on the repair of the affected tissue in a mouse model of cigarette smoke exposure, but by what pathways it achieves this is unknown. The present study aimed to identify differentially expressed genes between emphysematous mice treated with LGF to identify potential therapeutic targets for the treatment of pulmonary emphysema. The emphysema mouse model was induced by prolonged exposure to cigarette smoke. To determine the gene expression profile of the lung in smokers treated or not with LGF, lung messenger RNA gene expression was assessed with the Agilent Array platform. We carried out differentially expressed gene analysis, functional enrichment and validated in treated mouse lung samples. The treated group significantly improved lung function (35%) and emphysema level (20%), consistent with our previous published studies. Microarray analysis demonstrated 290 differentially expressed genes in total (2.0-fold over or lower expressed). Injury repair-associated genes and pathways were further enhanced in the lung of LGF treated mice. The expression trends of two genes (Zscan2 and Bag6) were different in emphysematous lungs treated with LGF compared to untreated lungs. Therefore, Zscan2 and Bag6 genes could play a role in regulating inflammation and the immune response in the lung that undergoes partial lung regeneration. However, further studies are necessary to demonstrate this causal relationship.
慢性阻塞性肺疾病是一种常见的慢性肺部疾病，其发病率不断增加。尽管经过多年的药物研究和批准，我们仍然无法阻止病情进展或恢复正常的肺功能。我们之前的研究表明，肝生长因子-LGF 对香烟烟雾暴露的小鼠模型中受影响组织的修复有作用，但它通过什么途径实现这一点尚不清楚。本研究旨在确定接受 LGF 治疗的肺气肿小鼠之间的差异表达基因，以鉴定治疗肺气肿的潜在治疗靶点。通过长期暴露于香烟烟雾来诱导肺气肿小鼠模型。为了确定接受或不接受 LGF 治疗的吸烟者的肺部基因表达谱，使用 Agilent Array 平台评估肺信使 RNA 基因表达。我们进行了差异表达基因分析、功能富集，并在处理后的小鼠肺样本中进行了验证。治疗组的肺功能（约 35%）和肺气肿水平（约 20%）显著改善，与我们之前发表的研究结果一致。微阵列分析显示，总共存在 290 个差异表达基因（表达上调或下调 2 倍）。损伤修复相关基因和途径在 LGF 治疗的小鼠肺部进一步增强。与未治疗的肺部相比，接受 LGF 治疗的肺气肿肺部中两个基因（Zscan2 和 Bag6）的表达趋势不同。因此，Zscan2 和 Bag6 基因可能在调节肺部分再生过程中的炎症和免疫反应中发挥作用。然而，需要进一步的研究来证明这种因果关系。
