Sarcopenia is attenuated by mairin in SAMP8 mice via the inhibition of FAPs fibrosis through the AMPK-TGF-ß-SMAD axis.
Gene
; 931: 148873, 2024 Dec 30.
Article
em En
| MEDLINE
| ID: mdl-39159793
ABSTRACT
Sarcopenia has become a prominent health problem among the elderly because of its adverse consequence, including physical disabilities and death. Fibro-adipogenic progenitors (FAPs) exhibit adipogenic and fibrogenic potencies and regulate skeletal muscle development, which plays important role in sarcopenia. Mairin, as an ingredient of Astragalus membranaceus, has the effect of anti-fibrosis. Therefore, we predicted that mairin targeted the fibrosis of FAPs and then affected sarcopenia. To verify our ideas, mairin (30 mg/kg/day or 60 mg/kg/day) was given to senescence accelerated mouse-prone 8 (SAMP8) mice by oral administration. Aging led to loss of weight, skeletal muscle mass, strength, and function, and an increase in muscle atrophy and fibrosis, while mairin administration inhibited physiological decline caused by aging. Similarly, mairin (20 µM or 40 µM) treatment enhanced FAP proliferation but blocked the differentiation into fibroblasts. Mechanically, mairin played an anti-fibrotic role via AMP-activated protein kinase-transforming growth factor beta-drosophila mothers against decapentaplegic protein (AMPK-TGF-ß-SMAD) axis, as evidenced by increased phosphorylation of AMPKα and decreased TGF-ß and phosphorylated-SMAD2/3. In addition, the potential target genes of mairin were explored by mRNA sequencing in our study. In conclusion, mairin may interfere with the AMPK/TGF-ß/SMAD pathway to repress the fibrosis of FAPs and eventually ameliorate sarcopenia.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrose
/
Transdução de Sinais
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Fator de Crescimento Transformador beta
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Proteínas Quinases Ativadas por AMP
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Sarcopenia
Limite:
Animals
Idioma:
En
Revista:
Gene
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China