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Identification of a novel immune-related transcriptional regulatory network in sarcopenia

BACKGROUND: Sarcopenia is highly prevalent in elderly individuals and has a significant adverse effect on their physical health and quality of life, but the mechanisms remain unclear. Studies have indicated that transcription factors (TFs) and the immune microenvironment play a vital role in skeleta...

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Autores principales: Zhang, Xianzhong, Zhu, Guanglou, Zhang, Fengmin, Yu, Dingye, Jia, Xuyang, Ma, Bingwei, Chen, Weizhe, Cai, Xinyu, Mao, Lingzhou, Zhuang, Chengle, Yu, Zhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10391869/
https://www.ncbi.nlm.nih.gov/pubmed/37525094
http://dx.doi.org/10.1186/s12877-023-04152-1
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author Zhang, Xianzhong
Zhu, Guanglou
Zhang, Fengmin
Yu, Dingye
Jia, Xuyang
Ma, Bingwei
Chen, Weizhe
Cai, Xinyu
Mao, Lingzhou
Zhuang, Chengle
Yu, Zhen
author_facet Zhang, Xianzhong
Zhu, Guanglou
Zhang, Fengmin
Yu, Dingye
Jia, Xuyang
Ma, Bingwei
Chen, Weizhe
Cai, Xinyu
Mao, Lingzhou
Zhuang, Chengle
Yu, Zhen
author_sort Zhang, Xianzhong
collection PubMed
description BACKGROUND: Sarcopenia is highly prevalent in elderly individuals and has a significant adverse effect on their physical health and quality of life, but the mechanisms remain unclear. Studies have indicated that transcription factors (TFs) and the immune microenvironment play a vital role in skeletal muscle atrophy. METHODS: RNA-seq data of 40 muscle samples were downloaded from the GEO database. Then, differentially expressed genes (DEGs), TFs(DETFs), pathways(DEPs), and the expression of immune gene sets were identified with limma, edgeR, GO, KEGG, ORA, GSVA, and ssGSEA. Furthermore, the results above were integrated into coexpression analysis by Pearson correlation analysis (PCA). Significant coexpression patterns were used to construct the immune-related transcriptional regulatory network by Cytoscape and potential medicine targeting the network was screened by Connectivity Map. Finally, the regulatory mechanisms and RNA expression of DEGs and DETFs were identified by multiple online databases and RT‒qPCR. RESULTS: We screened 808 DEGs (log2 fold change (FC) > 1 or <  − 1, p < 0.05), 4 DETFs (log2FC > 0.7 or <  − 0.7, p < 0.05), 304 DEPs (enrichment scores (ES) > 1 or <  − 1, p < 0.05), and 1208 differentially expressed immune genes sets (DEIGSs) (p < 0.01). Based on the results of PCA (correlation coefficient (CC) > 0.4 or <  − 0.4, p < 0.01), we then structured an immune-related network with 4 DETFs, 9 final DEGs, 11 final DEPs, and 6 final DEIGSs. Combining the results of online databases and in vitro experiments, we found that PAX5-SERPINA5-PI3K/Akt (CC ≤ 0.444, p ≤ 0.004) was a potential transcriptional regulation axis, and B cells (R = 0.437, p = 0.005) may play a vital role in this signal transduction. Finally, the compound of trichostatin A (enrichment = -0.365, specificity = 0.4257, p < 0.0001) might be a potential medicine for sarcopenia based on the PubChem database and the result of the literature review. CONCLUSIONS: We first identified immune-related transcriptional regulatory network with high-throughput RNA-seq data in sarcopenia. We hypothesized that PAX5-SERPIAN5-PI3K/Akt axis is a potential mechanism in sarcopenia and that B cells may play a vital role in this signal transduction. In addition, trichostatin A might be a potential medicine for sarcopenia. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12877-023-04152-1.
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spelling pubmed-103918692023-08-02 Identification of a novel immune-related transcriptional regulatory network in sarcopenia Zhang, Xianzhong Zhu, Guanglou Zhang, Fengmin Yu, Dingye Jia, Xuyang Ma, Bingwei Chen, Weizhe Cai, Xinyu Mao, Lingzhou Zhuang, Chengle Yu, Zhen BMC Geriatr Research Article BACKGROUND: Sarcopenia is highly prevalent in elderly individuals and has a significant adverse effect on their physical health and quality of life, but the mechanisms remain unclear. Studies have indicated that transcription factors (TFs) and the immune microenvironment play a vital role in skeletal muscle atrophy. METHODS: RNA-seq data of 40 muscle samples were downloaded from the GEO database. Then, differentially expressed genes (DEGs), TFs(DETFs), pathways(DEPs), and the expression of immune gene sets were identified with limma, edgeR, GO, KEGG, ORA, GSVA, and ssGSEA. Furthermore, the results above were integrated into coexpression analysis by Pearson correlation analysis (PCA). Significant coexpression patterns were used to construct the immune-related transcriptional regulatory network by Cytoscape and potential medicine targeting the network was screened by Connectivity Map. Finally, the regulatory mechanisms and RNA expression of DEGs and DETFs were identified by multiple online databases and RT‒qPCR. RESULTS: We screened 808 DEGs (log2 fold change (FC) > 1 or <  − 1, p < 0.05), 4 DETFs (log2FC > 0.7 or <  − 0.7, p < 0.05), 304 DEPs (enrichment scores (ES) > 1 or <  − 1, p < 0.05), and 1208 differentially expressed immune genes sets (DEIGSs) (p < 0.01). Based on the results of PCA (correlation coefficient (CC) > 0.4 or <  − 0.4, p < 0.01), we then structured an immune-related network with 4 DETFs, 9 final DEGs, 11 final DEPs, and 6 final DEIGSs. Combining the results of online databases and in vitro experiments, we found that PAX5-SERPINA5-PI3K/Akt (CC ≤ 0.444, p ≤ 0.004) was a potential transcriptional regulation axis, and B cells (R = 0.437, p = 0.005) may play a vital role in this signal transduction. Finally, the compound of trichostatin A (enrichment = -0.365, specificity = 0.4257, p < 0.0001) might be a potential medicine for sarcopenia based on the PubChem database and the result of the literature review. CONCLUSIONS: We first identified immune-related transcriptional regulatory network with high-throughput RNA-seq data in sarcopenia. We hypothesized that PAX5-SERPIAN5-PI3K/Akt axis is a potential mechanism in sarcopenia and that B cells may play a vital role in this signal transduction. In addition, trichostatin A might be a potential medicine for sarcopenia. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12877-023-04152-1. BioMed Central 2023-07-31 /pmc/articles/PMC10391869/ /pubmed/37525094 http://dx.doi.org/10.1186/s12877-023-04152-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Zhang, Xianzhong
Zhu, Guanglou
Zhang, Fengmin
Yu, Dingye
Jia, Xuyang
Ma, Bingwei
Chen, Weizhe
Cai, Xinyu
Mao, Lingzhou
Zhuang, Chengle
Yu, Zhen
Identification of a novel immune-related transcriptional regulatory network in sarcopenia
title Identification of a novel immune-related transcriptional regulatory network in sarcopenia
title_full Identification of a novel immune-related transcriptional regulatory network in sarcopenia
title_fullStr Identification of a novel immune-related transcriptional regulatory network in sarcopenia
title_full_unstemmed Identification of a novel immune-related transcriptional regulatory network in sarcopenia
title_short Identification of a novel immune-related transcriptional regulatory network in sarcopenia
title_sort identification of a novel immune-related transcriptional regulatory network in sarcopenia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10391869/
https://www.ncbi.nlm.nih.gov/pubmed/37525094
http://dx.doi.org/10.1186/s12877-023-04152-1
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