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

IF 4.4 4区 医学 Q1 GERIATRICS & GERONTOLOGY
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引用次数: 0

摘要

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

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.

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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.
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