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在……中与骨骼肌成熟和肥大相关的关键基因及生物学通路的鉴定

Identification of Key Genes and Biological Pathways Associated with Skeletal Muscle Maturation and Hypertrophy in , and .

作者信息

Mohammadinejad Fatemeh, Mohammadabadi Mohammadreza, Roudbari Zahra, Sadkowski Tomasz

机构信息

Department of Animal Science, Faculty of Agriculture, Shahid Bahonar University of Kerman, Kerman 7616914111, Iran.

Department of Animal Science, Faculty of Agriculture, University of Jiroft, Jiroft 7867155311, Iran.

出版信息

Animals (Basel). 2022 Dec 8;12(24):3471. doi: 10.3390/ani12243471.

DOI:10.3390/ani12243471
PMID:36552391
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9774933/
Abstract

The aim of the current study was to identify the major genes and pathways involved in the process of hypertrophy and skeletal muscle maturation that is common for Bos taurus, Ovis aries, and Sus scrofa species. Gene expression profiles related to Bos taurus, Ovis aries, and Sus scrofa muscle, with accession numbers GSE44030, GSE23563, and GSE38518, respectively, were downloaded from the GEO database. Differentially expressed genes (DEGs) were screened out using the Limma package of R software. Genes with Fold Change > 2 and an adjusted p-value < 0.05 were identified as significantly different between two treatments in each species. Subsequently, gene ontology and pathway enrichment analyses were performed. Moreover, hub genes were detected by creating a protein−protein interaction network (PPI). The results of the analysis in Bos taurus showed that in the period of 280 dpc−3-months old, a total of 1839 genes showed a significant difference. In Ovis aries, however, during the period of 135dpc−2-months old, a total of 486 genes were significantly different. Additionally, in the 91 dpc−adult period, a total of 2949 genes were significantly different in Sus scrofa. The results of the KEGG pathway enrichment analysis and GO function annotation in each species separately revealed that in Bos taurus, DEGs were mainly enriched through skeletal muscle fiber development and skeletal muscle contraction, and the positive regulation of fibroblast proliferation, positive regulation of skeletal muscle fiber development, PPAR signaling pathway, and HIF-1 signaling pathway. In Ovis aries, DEGs were mainly enriched through regulating cell growth, skeletal muscle fiber development, the positive regulation of fibroblast proliferation, skeletal muscle cell differentiation, and the PI3K-Akt signaling, HIF-1 signaling, and Rap1 signaling pathways. In Sus scrofa, DEGs were mainly enriched through regulating striated muscle tissue development, the negative regulation of fibroblast proliferation and myoblast differentiation, and the HIF-1 signaling, AMPK signaling, and PI3K-Akt signaling pathways. Using a Venn diagram, 36 common DEGs were identified between Bos taurus, Ovis aries, and Sus scrofa. A biological pathways analysis of 36 common DEGs in Bos taurus, Ovis aries, and Sus scrofa allowed for the identification of common pathways/biological processes, such as myoblast differentiation, the regulation of muscle cell differentiation, and positive regulation of skeletal muscle fiber development, that orchestrated the development and maturation of skeletal muscle. As a result, hub genes were identified, including PPARGC1A, MYOD1, EPAS1, IGF2, CXCR4, and APOA1, in all examined species. This study provided a better understanding of the relationships between genes and their biological pathways in the skeletal muscle maturation process.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c0/9774933/c640a3b69713/animals-12-03471-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c0/9774933/00afd8b57fd5/animals-12-03471-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c0/9774933/5769c0b199ae/animals-12-03471-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c0/9774933/c640a3b69713/animals-12-03471-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c0/9774933/00afd8b57fd5/animals-12-03471-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c0/9774933/5769c0b199ae/animals-12-03471-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52c0/9774933/c640a3b69713/animals-12-03471-g003.jpg
摘要

本研究的目的是确定参与牛、羊和猪物种共有的肥大和骨骼肌成熟过程的主要基因和途径。分别从GEO数据库下载了与牛、羊和猪肌肉相关的基因表达谱,登录号分别为GSE44030、GSE23563和GSE38518。使用R软件的Limma包筛选差异表达基因(DEG)。将每个物种中两种处理之间变化倍数>2且校正p值<0.05的基因鉴定为显著差异基因。随后,进行基因本体论和通路富集分析。此外,通过创建蛋白质-蛋白质相互作用网络(PPI)检测枢纽基因。牛的分析结果表明,在妊娠280天至3月龄期间,共有1839个基因存在显著差异。然而,在羊中,在妊娠135天至2月龄期间,共有486个基因存在显著差异。此外,在猪中,在妊娠91天至成年期,共有2949个基因存在显著差异。对每个物种单独进行的KEGG通路富集分析和GO功能注释结果表明,在牛中,DEG主要通过骨骼肌纤维发育、骨骼肌收缩以及成纤维细胞增殖的正调控、骨骼肌纤维发育的正调控、PPAR信号通路和HIF-1信号通路富集。在羊中,DEG主要通过调节细胞生长、骨骼肌纤维发育、成纤维细胞增殖的正调控、骨骼肌细胞分化以及PI3K-Akt信号通路、HIF-1信号通路和Rap1信号通路富集。在猪中,DEG主要通过调节横纹肌组织发育、成纤维细胞增殖和肌成纤维细胞分化的负调控以及HIF-1信号通路、AMPK信号通路和PI3K-Akt信号通路富集。使用维恩图,在牛、羊和猪之间鉴定出36个共同的DEG。对牛、羊和猪中36个共同DEG的生物学通路分析,确定了协调骨骼肌发育和成熟的共同通路/生物学过程,如肌成纤维细胞分化、肌肉细胞分化的调节以及骨骼肌纤维发育的正调控。结果,在所有检测物种中鉴定出枢纽基因,包括PPARGC1A、MYOD1、EPAS1、IGF2 CXCR4和APOA1。本研究有助于更好地理解骨骼肌成熟过程中基因与其生物学通路之间的关系。

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