4-辛基衣康酸(OI)是一种细胞可渗透的衣康酸衍生物。研究表明,在系统性硬化症中具有抗纤维化作用,OI也影响破骨细胞分化。本研究的目的是通过RNA-seq分析探索OI对成肌细胞分化影响的分子机制。
成肌细胞增殖,分化,在用各种浓度(2.5、10、25、50和100μmol/L)的OI处理的C2C12成肌细胞中检查肌肉调节因子。用PI3K-Akt激活剂IGF-1处理细胞以探索PI3K-Akt途径在肌源性分化的OI抑制中的作用。通过RNA-seq和随后的基因本体论(GO)进一步研究了OI在肌生成中的调控机制。京都基因和基因组百科全书(KEGG)和,基因集富集分析(GSEA)。
各种浓度的OI在细胞增殖过程中没有显示任何作用。在分化过程中,OI以剂量依赖性方式抑制成熟肌管肌球蛋白重链(MHC)和肌原蛋白标记的表达。OI通过抑制AKT1磷酸化影响MyoD调节的活性来抑制肌肉分化。KEGG富集分析和GSEA结果表明,OI在成肌分化过程中影响了多种代谢途径,包括PI3K-Akt信号,钙信号,和PPAR信号。
我们的研究拓宽了对肌源性分化的OI抑制的理解。OI通过靶向多种分子和途径发挥其功能,提供对OI整体效应的理解的新颖见解。
The 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.
Myoblast 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).
OI 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.
Our 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.