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

IF 4.4 4区 医学 Q1 GERIATRICS & GERONTOLOGY Biogerontology Pub Date : 2024-02-26 DOI:10.1007/s10522-024-10093-y
{"title":"The SGLT2 inhibitor empagliflozin inhibits skeletal muscle fibrosis in naturally aging male mice through the AMPKα/MMP9/TGF-β1/Smad pathway","authors":"","doi":"10.1007/s10522-024-10093-y","DOIUrl":null,"url":null,"abstract":"<h3>Abstact</h3> <p>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-β1. 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/TGFβ1/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/TGFβ1/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/TGFβ1/Smad signaling pathways.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"18 1","pages":""},"PeriodicalIF":4.4000,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biogerontology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10522-024-10093-y","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
引用次数: 0

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-β1. 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/TGFβ1/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/TGFβ1/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/TGFβ1/Smad signaling pathways.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
SGLT2抑制剂empagliflozin通过AMPKα/MMP9/TGF-β1/Smad途径抑制自然衰老雄性小鼠的骨骼肌纤维化
停用 随着年龄的增长,肌肉疏松症的发病率也会增加,最终导致一系列不良反应。然而,目前还缺乏治疗肌肉疏松症的有效药物。钠-葡萄糖协同转运体 2 抑制剂(SGLT2i)empagliflozin 在多个器官中显示出抗纤维化能力。本研究旨在确定empagliflozin能否改善自然衰老小鼠因肌肉疏松症诱发的骨骼肌纤维化。通过喂养 13 个月至 19 个月大的雄性小鼠,建立了自然衰老模型。通过用 TGF-β1 刺激骨骼肌成纤维细胞建立了纤维化模型。前肢握力测试评估了骨骼肌功能,并通过Western印迹、qPCR和免疫组化分析了COL1A1、COL3A1和α-SMA的表达水平。此外,还检测了 AMPKα/MMP9/TGFβ1/Smad 信号通路的水平。在自然衰老的小鼠中,骨骼肌功能下降,肌肉纤维化标志物表达增加,AMPKα表达下调,MMP9/TGFβ1/Smad信号通路上调。然而,使用empagliflozin治疗可逆转这一现象。在细胞水平,empagliflozin表现出类似的抗纤维化作用,而化合物C和siAMPKα会减弱这些作用。Empagliflozin 的抗纤维化作用可能与 AMPK/MMP9/TGFβ1/Smad 信号通路有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
相关文献
N-Acetyl Serotonin Provides Neuroprotective Effects by Inhibiting Ferroptosis in the Neonatal Rat Hippocampus Following Hypoxic Brain Injury.
IF 5.1 2区 医学Molecular NeurobiologyPub Date : 2023-11-01 DOI: 10.1007/s12035-023-03464-y
Xiaomei Yang, Yue Yang, Feng Gao, Kangping Lu, Chunling Wang
The role of trapidil on neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury
IF 2.5 3区 医学Early human developmentPub Date : 2008-04-01 DOI: 10.1016/j.earlhumdev.2007.06.005
Aytug Atici , Gulcin Bozlu , Ali Haydar Turhan , Ayse Polat , Ali Nayci , Cetin Okuyaz , Hakan Taskinlar
Role of immunoglobulin in neuronal apoptosis in a neonatal rat model of hypoxic ischemic brain injury.
IF 2.7 4区 医学Experimental and therapeutic medicinePub Date : 2014-03-01 DOI: 10.3892/etm.2014.1470
Salih Kalay, Osman Oztekin, Gönül Tezel, Hakan Aldemir, Emel Sahin, Sadi Köksoy, Mustafa Akçakuş, Nihal Oygur
来源期刊
Biogerontology
Biogerontology 医学-老年医学
CiteScore
8.00
自引率
4.40%
发文量
54
审稿时长
>12 weeks
期刊介绍: The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments. Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.
期刊最新文献
Chrysin alleviates the impeded neurogenesis in accelerated brain aging by D-galactose in rats. Distinguishing the intrinsic and extrinsic causes of changes in human mortality by examining life-table aging rate (LAR) trajectories through the lens of generalized Gompertz-Makeham law. Modelling orexinergic system in ageing in the African turquoise killifish. Neuroinflammation increases in old and oldest-old rats except for dura mater meningeal tissue with significant gender differences: a translational perspective. The crosstalk between CNS resident glial cells and peripheral immune cells is critical for age-dependent demyelination and subsequent remyelination.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1