The SGLT2 inhibitor empagliflozin inhibits skeletal muscle fibrosis in naturally aging male mice through the AMPKα/MMP9/TGF-β1/Smad pathway

作者全名："Huang, Qixuan; Chen, Jie; Liao, Siqi; Long, Jiangchuan; Fang, Ronghua; He, Yusen; Chen, Peiyun; Liu, Dongfang"

作者地址："[Huang, Qixuan; Chen, Jie; Long, Jiangchuan; Fang, Ronghua; He, Yusen; Chen, Peiyun; Liu, Dongfang] Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrinol, Chongqing 400010, Peoples R China; [Chen, Jie] Ninth Peoples Hosp Chongqing, Dept Endocrinol, Chongqing 400700, Peoples R China; [Liao, Siqi] Chongqing Med Univ, Affiliated Hosp 2, Dept Gastroenterol, Chongqing 400010, Peoples R China"

通信作者："Liu, DF (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrinol, Chongqing 400010, Peoples R China."

来源：BIOGERONTOLOGY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001171877000001

JCR分区：Q1

影响因子：4.4

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Empagliflozin; Sarcopenia; Fibrosis; AMPK alpha; TGF beta 1; Smad

摘要："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-beta 1. The Forelimb grip strength test assessed skeletal muscle function, and expression levels of COL1A1, COL3A1, and alpha-SMA were analyzed by western blot, qPCR, and immunohistochemistry. Additionally, levels of AMPK alpha/MMP9/TGF beta 1/Smad signaling pathways were examined. In naturally aging mice, skeletal muscle function declines, expression of muscle fibrosis markers increases, AMPK alpha expression is downregulated, and MMP9/TGF beta 1/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 siAMPK alpha. Empagliflozin exhibits anti-fibrotic effects, possibly associated with the AMPK/MMP9/TGF beta 1/Smad signaling pathways."

基金机构：Chongqing Municipal Health Commission

基金资助正文：No Statement Available