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大鼠肌肉中的转录谱:急性剧烈运动中的下调网络

Transcriptional profile in rat muscle: down-regulation networks in acute strenuous exercise.

作者信息

Felipe Stela Mirla da Silva, de Freitas Raquel Martins, Penha Emanuel Diego Dos Santos, Pacheco Christina, Martins Danilo Lopes, Alves Juliana Osório, Soares Paula Matias, Loureiro Adriano César Carneiro, Lima Tanes, Silveira Leonardo R, Ferraz Alex Soares Marreiros, de Souza Jorge Estefano Santana, Leal-Cardoso Jose Henrique, Carvalho Denise P, Ceccatto Vania Marilande

机构信息

Superior Institute of Biomedic Sciences, Universidade Estadual do Ceará, Fortaleza, Ceará, Brazil.

Digital Metropolis Institute, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.

出版信息

PeerJ. 2021 Apr 2;9:e10500. doi: 10.7717/peerj.10500. eCollection 2021.

Abstract

BACKGROUND

Physical exercise is a health promotion factor regulating gene expression and causing changes in phenotype, varying according to exercise type and intensity. Acute strenuous exercise in sedentary individuals appears to induce different transcriptional networks in response to stress caused by exercise. The objective of this research was to investigate the transcriptional profile of strenuous experimental exercise.

METHODOLOGY

RNA-Seq was performed with soleus muscle, submitted to strenuous physical exercise on a treadmill with an initial velocity of 0.5 km/h and increments of 0.2 km/h at every 3 min until animal exhaustion. Twenty four hours post-physical exercise, RNA-seq protocols were performed with coverage of 30 million reads per sample, 100 pb read length, paired-end, with a list of counts totaling 12816 genes.

RESULTS

Eighty differentially expressed genes (61 down-regulated and 19 up-regulated) were obtained. Reactome and KEGG database searches revealed the most significant pathways, for down-regulated gene set, were: PI3K-Akt signaling pathway, RAF-MAP kinase, P2Y receptors and Signaling by Erbb2. Results suggest PI3K-AKT pathway inactivation by Hbegf, Fgf1 and Fgr3 receptor regulation, leading to inhibition of cell proliferation and increased apoptosis. Cell signaling transcription networks were found in transcriptome. Results suggest some metabolic pathways which indicate the conditioning situation of strenuous exercise induced genes encoding apoptotic and autophagy factors, indicating cellular stress.

CONCLUSION

Down-regulated networks showed cell transduction and signaling pathways, with possible inhibition of cellular proliferation and cell degeneration. These findings reveal transitory and dynamic process in cell signaling transcription networks in skeletal muscle after acute strenuous exercise.

摘要

背景

体育锻炼是一种促进健康的因素,可调节基因表达并导致表型变化,其变化因运动类型和强度而异。久坐不动的个体进行急性剧烈运动似乎会诱导不同的转录网络以应对运动引起的压力。本研究的目的是调查剧烈实验性运动的转录谱。

方法

对比目鱼肌进行RNA测序,将其置于跑步机上进行剧烈体育锻炼,初始速度为0.5公里/小时,每3分钟增加0.2公里/小时,直至动物疲惫。体育锻炼后24小时,按照RNA测序方案进行操作,每个样本的覆盖度为3000万条读数,读长为100个碱基对,双末端测序,共计12816个基因的计数列表。

结果

获得了80个差异表达基因(61个下调和19个上调)。通过Reactome和KEGG数据库搜索发现,下调基因集最显著的途径是:PI3K-Akt信号通路、RAF-MAP激酶、P2Y受体和Erbb2信号传导。结果表明,Hbegf、Fgf1和Fgr3受体调节导致PI3K-AKT通路失活,从而抑制细胞增殖并增加细胞凋亡。在转录组中发现了细胞信号转导转录网络。结果表明,一些代谢途径表明剧烈运动诱导的编码凋亡和自噬因子的基因的调节情况,表明存在细胞应激。

结论

下调网络显示了细胞转导和信号通路,可能抑制细胞增殖和细胞变性。这些发现揭示了急性剧烈运动后骨骼肌细胞信号转导转录网络中的短暂和动态过程。

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