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糖尿病相关肌少症的全转录组景观揭示了新型 lncRNA Gm20743 的特定功能。

The Whole-transcriptome Landscape of Diabetes-related Sarcopenia Reveals the Specific Function of Novel lncRNA Gm20743.

机构信息

Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Diabetes & Metabolic Disease Laboratory, St. Vincent's Institute of Medical Research, Fitzroy, Melbourne, VIC, Australia.

出版信息

Commun Biol. 2022 Aug 1;5(1):774. doi: 10.1038/s42003-022-03728-8.

Abstract

While the exact mechanism remains unclear, type 2 diabetes mellitus increases the risk of sarcopenia which is characterized by decreased muscle mass, strength, and function. Whole-transcriptome RNA sequencing and informatics were performed on the diabetes-induced sarcopenia model of db/db mice. To determine the specific function of lncRNA Gm20743, the detection of Mito-Sox, reactive oxygen species, Ethynyl-2'-deoxyuridine, and myosin heavy chain was performed in overexpressed and knockdown-Gm20743 C2C12 cells. RNA-seq data and informatics revealed the key lncRNA-mRNA interactions and indicated a potential regulatory role of lncRNAs. We characterized three core candidate lncRNAs Gm20743, Gm35438, 1700047G03Rik, and their potential function. Furthermore, the results suggested lncRNA Gm20743 may be involved in regulating mitochondrial function, oxidative stress, cell proliferation, and myotube differentiation in skeletal muscle cells. These findings significantly improve our understanding of lncRNAs that may mediate muscle mass, strength, and function in diabetes and represent potential therapeutic targets for diabetes-induced sarcopenia.

摘要

虽然确切的机制尚不清楚,但 2 型糖尿病会增加肌少症的风险,其特征是肌肉质量、力量和功能下降。对 db/db 小鼠糖尿病性肌少症模型进行了全转录组 RNA 测序和信息学分析。为了确定 lncRNA Gm20743 的具体功能,在过表达和敲低-Gm20743 C2C12 细胞中检测了 Mito-Sox、活性氧、Ethynyl-2'-脱氧尿苷和肌球蛋白重链。RNA-seq 数据和信息学揭示了关键的 lncRNA-mRNA 相互作用,并表明 lncRNA 可能具有潜在的调节作用。我们对三个核心候选 lncRNA Gm20743、Gm35438、1700047G03Rik 及其潜在功能进行了表征。此外,研究结果表明,lncRNA Gm20743 可能参与调节骨骼肌细胞中线粒体功能、氧化应激、细胞增殖和肌管分化。这些发现显著提高了我们对可能介导糖尿病患者肌肉质量、力量和功能的 lncRNAs 的理解,代表了糖尿病性肌少症的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/058d/9343400/1ce9e2233e5a/42003_2022_3728_Fig1_HTML.jpg

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