Exercise-induced differential changes in gene expression among arterioles of skeletal muscles of obese rats

Exercise-induced differential changes in gene expression among arterioles of skeletal muscles of obese rats
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DOI:
10.1152/japplphysiol.00316.2015
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发表时间:
2015-09-15
影响因子:
3.3
通讯作者:
Davis, J. Wade
Davis, J. Wade
中科院分区:
医学2区
文献类型:
--
作者:
Laughlin, M. Harold;Padilla, Jaume;Davis, J. Wade

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使用新一代全转录组RNA测序(RNA-Seq)技术,我们评估了运动训练对从接受耐力运动训练计划的大冢龙埃文斯德岛肥胖(OLETF)大鼠的比目鱼肌和腓肠肌分离的骨骼肌小动脉中转录谱的影响(EX; n = 13)、间歇短跑训练计划(SPRINT; n = 14)或保持久坐(Sed; n = 12)。我们假设运动对腓肠肌小动脉的影响最大。结果表明,EX引起比目鱼肌和白色腓肠肌2a小动脉中基因表达的最大数量的变化,而供血动脉中几乎没有变化。相反,SPRINT引起供血动脉中基因表达的实质性变化。IPA经典途径分析显示,当跨血管分析时,18条途径的基因表达发生显著变化,并显示EX诱导所有检查的小动脉中以下基因的表达增加:Shc 1,沙漠刺猬蛋白(Dhh),腺苷酸环化酶4(Adcy 4),G蛋白结合蛋白,α(Gnat 1),和Bcl 2l 1,并降低泛素D(Ubd)和cAMP反应元件调节剂(Crem)的表达。EX增加内皮素转换酶(Ece 1),热休克蛋白90 b,Fkbp 5,和Cdcl 4 b在五个小动脉的表达。SPRINT对Crem、Dhh、Bcl 2l 1和Ubd表达的影响与EX相似。SPRINT还增加了所有5个小动脉中Nfkbia、Hspa 5、Tubb 2a和Tubb 2b以及Fkbp 5的表达,并增加了除比目鱼肌二级小动脉外所有小动脉中Gnat 1的表达。许多收缩和/或结构蛋白基因增加SPRINT在腓肠肌供血动脉,但相同的基因表现出减少腓肠肌红色小动脉的表达。我们的结论是,训练引起的小动脉基因表达模式的变化不同的肌纤维类型的组成和沿着小动脉树。
Using next-generation, transcriptome-wide RNA sequencing (RNA-Seq) technology we assessed the effects of exercise training on transcriptional profiles in skeletal muscle arterioles isolated from the soleus and gastrocnemius muscles of Otsuka Long Evans Tokushima Fatty (OLETF) rats that underwent an endurance exercise training program (EX; n = 13), interval sprint training program (SPRINT; n = 14), or remained sedentary (Sed; n = 12). We hypothesized that the greatest effects of exercise would be in the gastrocnemius arterioles. Results show that EX caused the largest number of changes in gene expression in the soleus and white gastrocnemius 2a arterioles with little to no changes in the feed arteries. In contrast, SPRINT caused substantial changes in gene expression in the feed arteries. IPA canonical pathway analysis revealed 18 pathways with significant changes in gene expression when analyzed across vessels and revealed that EX induces increased expression of the following genes in all arterioles examined: Shc1, desert hedgehog protein (Dhh), adenylate cyclase 4 (Adcy4), G protein binding protein, alpha (Gnat1), and Bcl2l1 and decreased expression of ubiquitin D (Ubd) and cAMP response element modulator (Crem). EX increased expression of endothelin converting enzyme (Ece1), Hsp90b, Fkbp5, and Cdcl4b in four of five arterioles. SPRINT had effects on expression of Crem, Dhh, Bcl2l1, and Ubd that were similar to EX. SPRINT also increased expression of Nfkbia, Hspa5, Tubb 2a and Tubb 2b, and Fkbp5 in all five arterioles and increased expression of Gnat1 in all but the soleus second-order arterioles. Many contractile and/or structural protein genes were increased by SPRINT in the gastrocnemius feed artery, but the same genes exhibited decreased expression in red gastrocnemius arterioles. We conclude that training-induced changes in arteriolar gene expression patterns differ by muscle fiber type composition and along the arteriolar tree.