Transcriptomic analysis of the regulatory mechanism of lipocalin-2 in silicosis inflammation
- VernacularTitle:基于转录组学探究脂质运载蛋白-2调控矽肺炎症的作用机制
- Author:
Yanan SUN
1
;
Yue ZHANG
1
;
Xinyao WANG
1
;
Fangze WAN
1
;
Heliang LIU
1
;
Hongli WANG
1
;
Sanqiao YAO
2
;
Hailan HE
1
Author Information
- Publication Type:Selectedarticle
- Keywords: silicosis; lipocalin-2; transcriptomics; inflammation; ZINC00640089
- From: Journal of Environmental and Occupational Medicine 2026;43(6):702-708
- CountryChina
- Language:Chinese
- Abstract: Background Lung tissue fibrosis caused by exposure to free silica (SiO2) dust is the core pathological feature of silicosis. Lipocalin-2 (LCN2), as a secreted glycoprotein, plays an important role in various inflammatory diseases, but its specific role in silicosis-induced inflammatory injury remains unclear. Objective To identify differentially expressed genes (DEGs) and enriched pathways in the lung tissues of rats with silicosis, and to explore the regulatory mechanism of LCN2 in silicosis inflammation. Methods Twenty specific pathogen-free male SD rats were randomly divided into a control group and a silicosis model group (n=10 per group). The silicosis model was established via a single intratracheal instillation of silicon dioxide (SiO2) suspension (50 mg), while the control group received an equal volume of normal saline. In vitro, NR8383 cells were divided into a control group and a SiO2 treatment group. Hematoxylin-eosin (HE) staining and Van Gieson (VG) staining were used to evaluate alveolar structure damage, inflammatory infiltration, and collagen deposition in the lung tissues. Transcriptomic sequencing was applied to screen for DEGs and enriched signaling pathways. Western blot was used to detect the protein expression of interleukin-6 (IL-6), E-cadherin (ECA), cluster of differentiation 36 (CD36), liver X receptor (LXR), ATP-binding cassette transporter A1 (ABCA1), and LCN2 in both rat lung tissues and NR8383 cells. Immunohistochemistry was used to further assess LCN2 expression and localization. Additionally, NR8383 cells were treated with the LCN2 inhibitor ZINC00640089 and assigned to four groups: control, ZINC00640089-only, SiO2, and SiO2+ZINC00640089. Western blot was used to evaluate the expression of LCN2, IL-6, and interleukin-1β (IL-1β). Results HE and VG staining revealed disorganized lung tissue structure, damaged alveolar walls, nodule formation, and increased collagen deposition in the silicosis model group compared to the controls. Transcriptomic analysis identified 2723 DEGs in the lung tissues of silicosis rats (312 down-regulated and 2411 up-regulated) with LCN2 expression being significantly up-regulated. These DEGs were primarily enriched in pathways related to the innate immune response, extracellular matrix (ECM)-receptor interaction, and inflammatory response. Immunohistochemical staining confirmed elevated LCN2 levels in the lung tissues of the model rats. Western blot demonstrated that the protein levels of IL-6, CD36, and LCN2 were significantly increased (P<0.05), whereas ABCA1 and ECA were significantly decreased in the silicosis group (P<0.05). Similarly, in SiO2-treated NR8383 cells, IL-6, CD36, and LCN2 expressions significantly increased (P<0.05), while ABCA1 and LXR significantly decreased (P<0.05). Compared with the SiO2 group, treatment with ZINC00640089 significantly reduced the expression levels of LCN2, IL-6, and IL-1β (P<0.05). Conclusion LCN2 is significantly upregulated in both the lung tissues of silicosis rats and SiO2-treated NR8383 cells. Inhibiting LCN2 expression effectively reduces the SiO2-induced inflammatory response, indicating that LCN2 serves as a potential therapeutic target for silicosis.
