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The SGLT2 inhibitor empagliflozin inhibits skeletal muscle fibrosis in naturally aging male mice through the AMPKα/MMP9/TGF-ß1/Smad pathway.
Huang, Qixuan; Chen, Jie; Liao, Siqi; Long, Jiangchuan; Fang, Ronghua; He, Yusen; Chen, Peiyun; Liu, Dongfang.
Afiliação
  • Huang Q; Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
  • Chen J; Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
  • Liao S; Department of Endocrinology, The Ninth People's Hospital of Chongqing, Chongqing, 400700, China.
  • Long J; Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
  • Fang R; Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
  • He Y; Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
  • Chen P; Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
  • Liu D; Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Biogerontology ; 25(3): 567-581, 2024 Jun.
Article em En | MEDLINE | ID: mdl-38403802
ABSTRACT
ABSTACT With advancing age, the incidence of sarcopenia increases, eventually leading to a cascade of adverse events. However, there is currently a lack of effective pharmacological treatment for sarcopenia. Sodium-glucose co-transporter 2 inhibitor (SGLT2i) empagliflozin demonstrates anti-fibrotic capabilities in various organs. This study aims to determine whether empagliflozin can improve skeletal muscle fibrosis induced by sarcopenia in naturally aging mice. A natural aging model was established by feeding male mice from 13 months of age to 19 months of age. A fibrosis model was created by stimulating skeletal muscle fibroblasts with TGF-ß1. The Forelimb grip strength test assessed skeletal muscle function, and expression levels of COL1A1, COL3A1, and α-SMA were analyzed by western blot, qPCR, and immunohistochemistry. Additionally, levels of AMPKα/MMP9/TGFß1/Smad signaling pathways were examined. In naturally aging mice, skeletal muscle function declines, expression of muscle fibrosis markers increases, AMPKα expression is downregulated, and MMP9/TGFß1/Smad signaling pathways are upregulated. However, treatment with empagliflozin reverses this phenomenon. At the cellular level, empagliflozin exhibits similar anti-fibrotic effects, and these effects are attenuated by Compound C and siAMPKα. Empagliflozin exhibits anti-fibrotic effects, possibly associated with the AMPK/MMP9/TGFß1/Smad signaling pathways.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Compostos Benzidrílicos / Fibrose / Envelhecimento / Transdução de Sinais / Músculo Esquelético / Metaloproteinase 9 da Matriz / Proteínas Smad / Fator de Crescimento Transformador beta1 / Proteínas Quinases Ativadas por AMP / Inibidores do Transportador 2 de Sódio-Glicose Limite: Animals Idioma: En Revista: Biogerontology Assunto da revista: GERIATRIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Compostos Benzidrílicos / Fibrose / Envelhecimento / Transdução de Sinais / Músculo Esquelético / Metaloproteinase 9 da Matriz / Proteínas Smad / Fator de Crescimento Transformador beta1 / Proteínas Quinases Ativadas por AMP / Inibidores do Transportador 2 de Sódio-Glicose Limite: Animals Idioma: En Revista: Biogerontology Assunto da revista: GERIATRIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Holanda