Therapeutic effects of MEL-dKLA by targeting M2 macrophages in pulmonary fibrosis.
Biomed Pharmacother
; 178: 117246, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-39096617
ABSTRACT
Idiopathic pulmonary fibrosis is a progressive lung disease characterized by excessive extracellular matrix accumulation and myofibroblast proliferation with limited treatment options available. M2 macrophages are pivotal in pulmonary fibrosis, where they induce the epithelial-to-mesenchymal and fibroblast-to-myofibroblast transitions. In this study, we evaluated whether MEL-dKLA, a hybrid peptide that can eliminate M2 macrophages, could attenuate pulmonary fibrosis in a cell co-culture system and in a bleomycin-induced mouse model. Our findings demonstrated that the removal of M2 macrophages using MEL-dKLA stimulated reprogramming to an antifibrotic environment, which effectively suppressed epithelial-to-mesenchymal and fibroblast-to-myofibroblast transition responses in lung epithelial and fibroblast cells and reduced extracellular matrix accumulation both in vivo and in vitro. Moreover, MEL-dKLA exhibited antifibrotic efficacy without damaging tissue-resident macrophages in the bleomycin-induced mouse model. Collectively, our findings suggest that MEL-dKLA may be a new therapeutic option for the treatment of idiopathic pulmonary fibrosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bleomicina
/
Fibrose Pulmonar Idiopática
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Macrófagos
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article