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

Yu, Jing; Loh, Kim; Yang, Huifeng; Du, Meng-ran; Wu, Yongxin; Liao, Zhiyin; Guo, Ai; Yang, Yunfei; Chen, Bin; Zhao, Yutong; Chen, Jinliang; Zhou, Jing; Sun, Yue; Xiao, Qian

doi:10.1038/s42003-022-03728-8

Cited by 9 publications

(5 citation statements)

References 69 publications

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“…Early activation of lncRNA Pvt1 following muscle atrophy affects mitochondrial respiration and morphology and influences autophagy and apoptosis related to mitochondrial conformation and myofiber size, and thus targeting lncRNA Pvt1 may be a viable therapeutic target for muscle atrophy [ 279 ]. lncRNA Gm20743 may be involved in regulating mitochondrial function, oxidative stress, cell proliferation and myotube differentiation in skeletal muscle cells, and may be a potential therapeutic target for diabetes-induced sarcopenia [ 280 ]. Taken together, these genes and non-coding RNAs would be novel targets for targeting mitochondrial dysfunction in the treatment of muscle atrophy.…”

Section: Therapeutic Strategies Targeting Mitochondria For Skeletal M...mentioning

confidence: 99%

Mitochondrial dysfunction: roles in skeletal muscle atrophy

Chen¹,

Ji²,

Liu³

et al. 2023

J Transl Med

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Mitochondria play important roles in maintaining cellular homeostasis and skeletal muscle health, and damage to mitochondria can lead to a series of pathophysiological changes. Mitochondrial dysfunction can lead to skeletal muscle atrophy, and its molecular mechanism leading to skeletal muscle atrophy is complex. Understanding the pathogenesis of mitochondrial dysfunction is useful for the prevention and treatment of skeletal muscle atrophy, and finding drugs and methods to target and modulate mitochondrial function are urgent tasks in the prevention and treatment of skeletal muscle atrophy. In this review, we first discussed the roles of normal mitochondria in skeletal muscle. Importantly, we described the effect of mitochondrial dysfunction on skeletal muscle atrophy and the molecular mechanisms involved. Furthermore, the regulatory roles of different signaling pathways (AMPK-SIRT1-PGC-1α, IGF-1-PI3K-Akt-mTOR, FoxOs, JAK-STAT3, TGF-β-Smad2/3 and NF-κB pathways, etc.) and the roles of mitochondrial factors were investigated in mitochondrial dysfunction. Next, we analyzed the manifestations of mitochondrial dysfunction in muscle atrophy caused by different diseases. Finally, we summarized the preventive and therapeutic effects of targeted regulation of mitochondrial function on skeletal muscle atrophy, including drug therapy, exercise and diet, gene therapy, stem cell therapy and physical therapy. This review is of great significance for the holistic understanding of the important role of mitochondria in skeletal muscle, which is helpful for researchers to further understanding the molecular regulatory mechanism of skeletal muscle atrophy, and has an important inspiring role for the development of therapeutic strategies for muscle atrophy targeting mitochondria in the future.

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Section: Therapeutic Strategies Targeting Mitochondria For Skeletal M...mentioning

confidence: 99%

Mitochondrial dysfunction: roles in skeletal muscle atrophy

Chen¹,

Ji²,

Liu³

et al. 2023

J Transl Med

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“…MiR-214-3p, as a novel member of the miRNA family, has been found to be involved in traumatic fractures of the brain, tumors, osteoarthritis, endothelial cell injury of coronary heart disease, myocardial cell fibrosis and other aspects [ 30 ]. However, the role of miR-214-3p in AIS and neuronal injury has not been reported.…”

Section: Discussionmentioning

confidence: 99%

The lncRNA lnc_AABR07044470.1 promotes the mitochondrial-damaged inflammatory response to neuronal injury via miR-214-3p/PERM1 axis in acute ischemic stroke

Wang,

Li,

Qian

et al. 2024

Mol Biol Rep

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Purpose We investigated the role of lnc_AABR07044470.1 on the occurrence and development of acute ischemic stroke (AIS) and neuronal injury by targeting the miR-214-3p/PERM1 axis to find a novel clinical drug target and prediction and treatment of AIS. Methods The mouse AIS animal model was used in vivo experiments and hypoxia/reoxygenation cell model in vitro was established. Firstly, infarction volume and pathological changes of mouse hippocampal neurons were detected using HE staining. Secondly, rat primary neuron apoptosis was detected by flow cytometry assay. The numbers of neuron, microglia and astrocytes were detected using immunofluorescence (IF). Furthermore, binding detection was performed by bioinformatics database and double luciferase reporter assay. Lnc_AABR07044470.1 localization was performed using fluorescence in situ hybridization (FISH).Lnc_AABR07044470.1, miR-214-3pand PERM1mRNA expression was performed using RT-qPCR. NLRP3, ASC, Caspase-1 and PERM1 protein expression was performed using Western blotting. IL-1β was detected by ELISA assay. Results Mouse four-vessel occlusion could easily establish the animal model, and AIS animal model had an obvious time-dependence. HE staining showed that, compared with the sham group, infarction volume and pathological changes of mouse hippocampal neurons were deteriorated in the model group. Furthermore, compared with the sham group, neurons were significantly reduced, while microglia and astrocytes were significantly activated. Moreover, the bioinformatics prediction and detection of double luciferase reporter confirmed the binding site of lnc_AABR07044470.1 to miR-214-3p and miR-214-3p to Perm1. lnc_AABR07044470.1 and PERM1 expression was significantly down-regulated and miR-214-3pexpression was significantly up-regulated in AIS animal model in vivo. At the same time, the expression of inflammasome NLRP3, ASC, Caspase-1 and pro-inflammatory factor IL-1β was significantly up-regulated in vivo and in vitro. The over-expression of lnc_AABR07044470.1 and miR-214-3p inhibitor could inhibit the neuron apoptosis and the expression of inflammasome NLRP3, ASC, Caspase-1 and pro-inflammatory factor IL-1β and up-regulate the expression of PERM1 in vitro. Finally, over-expression of lnc_AABR07044470.1 and miR-214-3p inhibitor transfected cell model was significant in relieving the AIS and neuronal injury. Conclusion Lnc_AABR07044470.1 promotes inflammatory response to neuronal injury via miR-214-3p/PERM1 axis in AIS.

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“…In our study, we utilized a severe obesity and diabetes db/db mouse model, in which the manifestation of sarcopenia was confirmed. Since the atrophy of type II fibers, such as GM, appears to be more prevalent in T2DM-related sarcopenia, 13 proteomics analysis was performed on the GM from db/db mice and littermate control db/m mice. Our study showed that the identified DEPs were significantly enriched in metabolic pathways, particularly pathways linked to lipid metabolism.…”

Section: ■ Discussionmentioning

confidence: 99%

“…Skeletal muscle serves as the primary tissue responsible for glucose disposal, accounting for up to 80% of insulin-stimulated glucose disposal . Impaired insulin-stimulated glucose disposal in skeletal muscle, a condition known as IR, is considered a predominant contributor to the development of T2DM. , Given the role of skeletal muscle IR in diabetes, various “omics” analyses of skeletal muscles from diabetic animal models or patients with T2DM, including transcriptome, proteome, and metabolome analyses, have been conducted to investigate the molecular mechanisms involved in the progression of T2DM. Nevertheless, these studies have largely focused on the mechanisms by which dysregulated metabolism in skeletal muscle contributes to diabetes, and the disease model of these studies involved diabetes alone without recognizing the comorbid occurrence of sarcopenia.…”

Section: Introductionmentioning

confidence: 99%

Proteomics Analysis Provides Insights into the Role of Lipid Metabolism in T2DM-Related Sarcopenia

Wu,

Wang,

Zhuang

et al. 2024

ACS Omega

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Sarcopenia has been recognized as an emerging complication of type 2 diabetes mellitus (T2DM). Currently, the pathogenesis of T2DM-related sarcopenia remains unclear. The aim of this study was to investigate the molecular mechanisms and potential therapeutic targets for T2DM-related sarcopenia. In this study, a T2DM-related sarcopenia mouse model was established using db/db mice. Proteins extracted from the gastrocnemius muscles of db/db mice and littermate control db/m mice were analyzed by a 4D label-free quantitative proteomics approach. A total of 131 upregulated and 68 downregulated proteins were identified as differentially expressed proteins (DEPs). Bioinformatics analysis revealed that DEPs were significantly enriched in lipid metabolism. Protein−protein interaction network analysis revealed that six hub proteins, including ACOX1, CPT2, ECI2, ACADVL, ACADL, and ECH1, were involved in the fatty acid oxidation. The hub protein-transcription factor-miRNA network was also constructed using the NetworkAnalyst tool. Finally, the hub proteins were validated by Western blotting and immunohistochemistry and further confirmed to be significantly negatively correlated with muscle mass and grip strength. Our study suggested that lipid metabolism, especially excessive fatty acid oxidation, may be a crucial contributor to the progression of T2DM-related sarcopenia and a common cause of the inter-relationship between T2DM and sarcopenia. Targeting lipid metabolism may be a promising therapeutic strategy for T2DM-related sarcopenia.

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

Cited by 9 publications

References 69 publications

Mitochondrial dysfunction: roles in skeletal muscle atrophy

Mitochondrial dysfunction: roles in skeletal muscle atrophy

The lncRNA lnc_AABR07044470.1 promotes the mitochondrial-damaged inflammatory response to neuronal injury via miR-214-3p/PERM1 axis in acute ischemic stroke

Proteomics Analysis Provides Insights into the Role of Lipid Metabolism in T2DM-Related Sarcopenia

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