Investigating rutin as a potential transforming growth factor-β type I receptor antagonist for the inhibition of bleomycin-induced lung fibrosis.
SMAD
TGF-β
TβRI
lung fibrosis
rutin
Journal
BioFactors (Oxford, England)
ISSN: 1872-8081
Titre abrégé: Biofactors
Pays: Netherlands
ID NLM: 8807441
Informations de publication
Date de publication:
25 Nov 2023
25 Nov 2023
Historique:
received:
25
05
2023
accepted:
26
08
2023
pubmed:
26
11
2023
medline:
26
11
2023
entrez:
25
11
2023
Statut:
aheadofprint
Résumé
Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition characterized by the abnormal regulation of extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). In this study, we investigated the potential of rutin, a natural flavonoid, in attenuating transforming growth factor-β (TGF-β)-induced ECM regulation and EMT through the inhibition of the TGF-β type I receptor (TβRI)-mediated suppressor of mothers against decapentaplegic (SMAD) signaling pathway. We found that non-toxic concentrations of rutin attenuated TGF-β-induced ECM-related genes, including fibronectin, elastin, collagen 1 type 1, and TGF-β, as well as myoblast differentiation from MRC-5 lung fibroblast cells accompanied by the downregulation of α-smooth muscle actin. Rutin also inhibited TGF-β-induced EMT processes, such as wound healing, migration, and invasion by regulating EMT-related gene expression. Additionally, rutin attenuated bleomycin-induced lung fibrosis in mice, thus providing a potential therapeutic option for IPF. The molecular docking analyses in this study predict that rutin occludes the active site of TβRI and inhibits SMAD-mediated fibrotic signaling pathways in lung fibrosis. These findings highlight the potential of rutin as a promising anti-fibrotic prodrug for lung fibrosis and other TGF-β-induced fibrotic and cancer-related diseases; however, further studies are required to validate its safety and effectiveness in other experimental models.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Korea Environmental Industry and Technology Institute
ID : 2021003420002
Organisme : National Research Foundation of Korea
ID : 2021R1F1A1048085
Informations de copyright
© 2023 International Union of Biochemistry and Molecular Biology.
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