Ac-SDKP antagonizes lung fibrosis through EGFR/STAT3 pathway in silicosis rats
10.3760/cma.j.cn121094-20240614-00272
- VernacularTitle:Ac-SDKP通过EGFR/STAT3途径拮抗矽肺大鼠肺脏纤维化
- Author:
Wenli LI
1
;
Lu LIU
1
;
Yi HE
1
;
Nana YAO
1
;
Haijing DENG
1
;
Ye QIAN
1
Author Information
1. 华北理工大学基础医学院，河北省慢性疾病基础医学重点实验室，唐山市老年慢性病临床基础研究重点实验室，唐山 063210
- Publication Type:Journal Article
- Keywords:
Silicosis;
N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP);
Epidermal Growth Factor Receptor (EGFR);
Signal Transducer and Activator of Transcription 3 (
- From:
Chinese Journal of Industrial Hygiene and Occupational Diseases
2025;43(10):721-727
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To examine the regulatory effects of a potential antifibrotic tetrapeptide called N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on the expression of epidermal growth factor (EGFR) and signal transducer and activator of transcription 3 (STAT3) in lung tissues with fibrosis induced by silicosis in rats. This study aims to explore the potential therapeutic benefits of Ac-SDKP in the prevention and treatment of fibrotic lung diseases associated with silicosis.Methods:In January 2024, disease targets and Ac-SDKP active ingredients were predicted through GeneCards (https://www.genecards.org) and OMIM (https://www.omim.org) databases. Using R 4.2.1 software, we identified overlapping targets between pulmonary fibrosis and AC-SDKP. Cytoscape 3.10.2 was employed to visualize interactions between active chemical components and these targets, followed by GO enrichment analysis and KEGG pathway analysis using R 4.2.1. Forty healthy adult Wistar rats were selected to establish silicosis models through single-dose gavage with 50 mg/ml silica suspension (1. 0 ml per rat). The rats were randomly divided into four groups: model control group (4 weeks), silicosis model group (4 weeks), Ac-SDKP preventive treatment group (acquired via intraperitoneal injection of a micro-release pump containing Ac-SDKP [800 μg/ (kg·d) ] during modeling, maintained for 4 weeks), and Ac-SDKP anti-fibrosis treatment group (acquired via intraperitoneal injection of the same pump after 2 weeks of modeling, continued maintenance for 2 weeks). Each group contained 10 rats. The pathological changes in rat lung tissues were observed. Western blot technology was used to detect the protein expression levels of α-smooth muscle actin (α-SMA), epidermal growth factor receptor (EGFR), signal transduction and activation transcription factor 3 (STAT 3), caspase 3, and caspase 8 in lung tissues. Immunohistochemical techniques were employed to assess the expressions of EGFR, STAT3, caspase 3, and caspase 8. Overall differences between groups were compared using one-way ANOVA.Results:Compared with the control group in the silicosis model, rats in the 4-week group exhibited significant fibrotic nodules. The lung tissues of these rats showed statistically significant increases in α-SMA, EGFR, STAT 3, Caspase 3, and Caspase 8 protein expression ( P<0.05). In contrast, the Ac-SDKP prevention and anti-fibrosis treatment group demonstrated markedly reduced expression levels of these proteins compared to the 4-week silicosis model group, with statistically significant differences ( P<0.05). Immunohistochemical staining revealed that brownish-yellow expression of EGFR, STAT3, Caspase3, and Caspase8 was significantly enhanced in silicotic nodules within the silicosis model group. Conversely, this brownish-yellow expression was notably decreased in the Ac-SDKP prevention and anti-fibrosis treatment group compared to the 4-week silicosis model group. Conclusion:Ac-SDKP may exert antifibrotic effects on the lungs of rats with silicosis by regulating the EGFR/STAT3 pathway.
