RNA-seq transcriptomic analysis of 4-octyl itaconate repressing myogenic differentiation.
RNA-seq transcriptomic analysis of 4-octyl itaconate repressing myogenic differentiation.
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DOI：
10.1016/j.abb.2022.109420
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发表时间：
2022-09
影响因子：
3.9
通讯作者：
Lili Wang;Zheng Chen;Yulan Feng;Rongrong Wang;Xiaohui Bai;Weihua Liu;Dawei Wang
中科院分区：
文献类型：
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作者：
Lili Wang;Zheng Chen;Yulan Feng;Rongrong Wang;Xiaohui Bai;Weihua Liu;Dawei Wang
BackgroundThe 4-octyl itaconate (OI) is a type of cell-permeable itaconate derivative. Studies have shown that with an anti-fibrotic effect in systemic sclerosis, the OI also affects osteoclast differentiation. The aim of this study was to explore the molecular mechanisms underlying the effects of OI on myoblast differentiation by RNA-seq analysis.MethodsMyoblast proliferation, differentiation, and muscle regulatory factors were examined in C2C12 myoblasts treated with OI of various concentrations (2.5, 10, 25, 50, and 100 μmol/L). Cells were treated with the PI3K-Akt activator IGF-1 to explore the role of the PI3K-Akt pathway in OI inhibition of myogenic differentiation. The regulatory mechanisms of OI in myogenesis were further investigated by RNA-seq and subsequent gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) and, gene set enrichment analysis (GSEA).ResultsOI of various concentrations did not show any effect during cell proliferation. During differentiation, OI inhibited the expressions of the marker of mature myotubes myosin heavy chain (MHC) and myogenin in a dose-dependent manner. OI inhibited muscle differentiation by affecting MyoD-regulated activity through inhibition of AKT1 phosphorylation. The results of the KEGG enrichment analysis and GSEA showed that OI affected multiple metabolic pathways during myogenic differentiation, including PI3K-Akt signaling, calcium signaling, and PPAR signaling.ConclusionsOur study broadens the understanding of the OI inhibition of myogenic differentiation. OI plays its functions by targeting multiple molecules and pathways, providing novel insights into the understanding of the overall effect of OI.
