Forkhead box protein A1 promotes macrophage M1 polarization and exacerbates chronic obstructive pulmonary disease by activating the nuclear factor-kappa B signaling pathway

Jiang Caiyu; Yang Yan

doi:10.13406/j.cnki.cyxb.003877

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Forkhead box protein A1 promotes macrophage M1 polarization and exacerbates chronic obstructive pulmonary disease by activating the nuclear factor-kappa B signaling pathway

Basic research | 更新时间：2026-10-26

- Forkhead box protein A1 promotes macrophage M1 polarization and exacerbates chronic obstructive pulmonary disease by activating the nuclear factor-kappa B signaling pathway
- Journal of Chongqing Medical University Vol. 51, Issue 10, Pages: 1479-1486(2026)
- 作者机构：
  
  四川省医学科学院·四川省人民医院/电子科技大学附属医院呼吸与危重症医学科，成都 610000
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003877
  CLC： R563
- Received：13 January 2025，
  
  Revised：2025-04-17，
  
  Accepted：18 April 2025，
  
  Published：28 October 2026
- 稿件说明：
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蒋才玉,杨雁.FOXA1通过激活NF-κB信号通路促进巨噬细胞M1极化加剧慢性阻塞性肺病[J].重庆医科大学学报,2026,51(10):1479-1486.

Jiang Caiyu,Yang Yan.Forkhead box protein A1 promotes macrophage M1 polarization and exacerbates chronic obstructive pulmonary disease by activating the nuclear factor-kappa B signaling pathway[J].Journal of Chongqing Medical University,2026,51(10):1479-1486.
蒋才玉,杨雁.FOXA1通过激活NF-κB信号通路促进巨噬细胞M1极化加剧慢性阻塞性肺病[J].重庆医科大学学报,2026,51(10):1479-1486. DOI： 10.13406/j.cnki.cyxb.003877.

Jiang Caiyu,Yang Yan.Forkhead box protein A1 promotes macrophage M1 polarization and exacerbates chronic obstructive pulmonary disease by activating the nuclear factor-kappa B signaling pathway[J].Journal of Chongqing Medical University,2026,51(10):1479-1486. DOI： 10.13406/j.cnki.cyxb.003877.

摘要

目的

探索叉头框蛋白A1（forkhead box protein A1，FOXA1）在慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）中的作用，从而进一步揭示慢性阻塞性肺病的潜在机制。

方法

采用香烟烟雾暴露法建立慢性阻塞性肺病小鼠模型，测定小鼠肺功能。通过苏木精、伊红染色和马松三色染色观察肺组织病理情况。通过酶联免疫吸附法测定炎症因子肿瘤坏死因子α（tumor necrosis factor-α，TNF-α）、白细胞介素1β（interleukin-1β，IL-1β）、白细胞介素6（interleukin-6，IL-6）含量。通过实时荧光定量聚合酶链式反应（polymerase chain reaction，PCR）或蛋白质印迹检测叉头框蛋白A1（forkhead box protein A1，FOXA1）、M1和M2巨噬细胞标志物诱导型一氧化氮合酶（induced nitric oxide synthase，iNOS）和分化群206（cluster of differentiation 206，CD206）和核因子-κB（nuclear factor-kappa B，NF-κB）信号通路相关蛋白的表达水平。

结果

FOXA1在慢性阻塞性肺病小鼠中表达上调（

=11.760，

0.001）。下调FOXA1可以减少肺组织损伤和纤维化，抑制巨噬细胞M1极化，促进巨噬细胞M2极化，减少炎症因子TNF-α（

=5.356，

0.001）、IL-1β（

=5.707，

0.001）和IL-6（

=7.668，

0.001）含量。此外，本研究还发现，下调FOXA1可以抑制NF-κB信号通路激活。

结论

FOXA1通过激活NF-κB信号通路促进巨噬细胞M1极化加剧慢性阻塞性肺病。

Abstract

Objective

To investigate the role of forkhead box protein A1（FOXA1

）

in chronic obstructive pulmonary disease（COPD） and the potential mechanism of COPD.

Methods

The method of cigarette smoke exposure was used to establish a mouse model of COPD，and the lung function of mice was measured. HE staining and Masson’s trichrome staining were used to observe the pathological changes of lung tissue；ELISA was used to measure the levels of the inflammatory factors tumor necrosis factor-α（TNF-α），interleukin-1β（IL-1β），and interleukin-6（IL-6）； quantitative real-time PCR or Western blotting was used to measure the expression levels of FOXA1，M1 and M2 macrophage markers（induced nitric oxide synthase［iNOS］ and cluster of differentiation 206［CD206］），and proteins associated with the nuclear factor-kappa B（NF-κB） signaling pathway.

Results

FOXA1 was upregulated in COPD mice （

=11.760，

0.001）. Downregulation of FOXA1 could reduce lung tissue damage and fibrosis，inhibit macrophage M1 polarization，promote macrophage M2 polarization，and reduce the levels of the inflammatory factors TNF-α（

=5.356，

0.001），IL-1β（

=5.707，

0.001），and IL-6（

=7.668，

0.001）. In addition，this study also showed that downregulation of FOXA1 could inhibit the activation of the NF-κB signaling pathway.

Conclusion

FOXA1 promotes macrophage M1 polarization and exacerbates COPD by activating the NF-κB signaling pathway.

关键词

Keywords

references

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