Molecular association between aging and idiopathic pulmonary fibrosis pathogenesis
10.3969/j.issn.1005-4847.2025.10.001
- VernacularTitle:衰老与特发性肺纤维化的相关性及关联的分子机制
- Author:
Shuqing LI
1
;
Yanfang WANG
;
Lisha MO
;
Liangji LIU
;
Shiwen KE
Author Information
1. 江西中医药大学,南昌 330004
- Publication Type:Journal Article
- Keywords:
pulmonary fibrosis;
idiopathic pulmonary fibrosis;
aging;
transcriptomics
- From:
Acta Laboratorium Animalis Scientia Sinica
2025;33(10):1403-1411
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the correlation between aging and idiopathic pulmonary fibrosis(IPF)and reveal the underlying molecular mechanisms.Methods IPF models were established using young(2-month-old)and aged(18-month-old)C57BL/6J mice by intratracheal instillation of bleomycin(BLM)hydrochloride(2.5 mg/kg)after fully exposing the trachea.The control groups received an equal volume of saline administered in the same manner.Mice were divided randomly into four groups:a young control(Ctrl-Y)group,young model(IPF-Y)group,aged control(Ctrl-A)group,and aged model(IPF-A)group.Histopathological changes were evaluated by hematoxylin-eosin and Masson staining.Collagen type Ⅰ alpha 1 chain(COL1A1),α-smooth muscle actin(SMA),and fibronectin(FN)expression were detected by immunohistochemistry.Cell senescence was detected by senescence-associated beta-galactosidase(SA-β-Gal)staining.Differentially expressed genes were detected by transcrip tome sequencing,followed by gene ontology functional annotation(GO)and kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.Core gene expression was validated by quantitative reverse transcription-polymerase chain reaction.Results The fibrosis score was significantly higher in the IPF-A group compared with the IPF-Y group(P＜0.05).Expression levels of α-SMA,and FN were significantly upregulated in the IPF-A group versus the IPF-Y group by 36％,and 25％,respectively(P＜0.05).The SA-β-Gal-positive area indicating senescence was significantly larger in the IPF-A group than in the IPF-Y group.Fifty-five senescence-IPF interactive genes were identified,among which Cdkn1a,MMP3,and Pdcd1 were synergistically upregulated in the IPF-A group(P＜0.05).KEGG analysis revealed the activation of signaling pathways such as extracellular matrix(ECM)-receptor interaction,phagosome,cytokine-cytokine receptor interaction,efferocytosis,and PI3K-Akt(FDR＜0.05).Conclusions aging promotes IPF progression,which induces lung tissue senescence.The underlying mechanism may involve ECM remodeling driven by immunosenescence,inflammatory accumulation,and metabolic disorders.
