Activating transcription factor 3 attenuates chemokine and cytokine expression in mouse skeletal muscle after exercise and facilitates molecular adaptation to endurance training
Activating transcription factor 3 attenuates chemokine and cytokine expression in mouse skeletal muscle after exercise and facilitates molecular adaptation to endurance training
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DOI：
10.1096/fj.201600987r
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发表时间：
2017-02-01
期刊：
影响因子：
4.8
通讯作者：
Francaux, Marc
中科院分区：
文献类型：
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作者：
Fernandez-Verdejo, Rodrigo;Vanwynsberghe, Aline M.;Francaux, Marc
转录激活因子（ATF）3在病理环境下调节多种组织中炎症相关基因的表达。在骨骼肌中，atf 3的表达在运动后增加，但其靶基因仍然未知。我们的目的是确定这些基因，并确定ATF 3对肌肉适应训练的影响。在休息时、运动后和训练后分析ATF 3敲除（ATF 3-KO）小鼠和对照小鼠的骨骼肌。在静息肌肉中，酶活性或纤维类型的基因型之间没有差异。运动后，在四头肌中的微阵列分析揭示了ATF 3影响调节趋化性和趋化因子/细胞因子活性的基因。定量PCR结果显示，ATF 3-KO小鼠股四头肌中趋化因子C-C motif ligand（ccl）8和C-X-C motif ligand（cxcl）13的mRNA水平高于对照组。在比目鱼肌中观察到ccl 9和cxcl 13也是如此。此外，在比目鱼肌中，ccl 2、白细胞介素（il）6、il 1和分化簇（cd）68 mRNA水平仅在ATF 3-KO小鼠运动后增加。耐力训练增加了对照小鼠四头肌中己糖激酶-2、激素敏感脂肪酶、谷胱甘肽过氧化物酶-1和肌球蛋白重链IIa的基础mRNA水平，但在ATF 3-KO小鼠中没有。总之，ATF 3减弱了运动后炎症相关基因的表达，从而促进了分子对训练的适应。
Activating transcription factor (ATF)3 regulates the expression of inflammation-related genes in several tissues under pathological contexts. In skeletal muscle, atf3 expression increases after exercise, but its target genes remain unknown. We aimed to identify those genes and to determine the influence of ATF3 on muscle adaptation to training. Skeletal muscles of ATF3-knockout (ATF3-KO) and control mice were analyzed at rest, after exercise, and after training. In resting muscles, there was no difference between genotypes in enzymatic activities or fiber type. After exercise, a microarray analysis in quadriceps revealed ATF3 affects genes modulating chemotaxis and chemokine/cytokine activity. Quantitative PCR showed that the mRNA levels of chemokine C-C motif ligand (ccl)8 and chemokine C-X-C motif ligand (cxcl)13 were higher in quadriceps of ATF3-KO mice than in control mice. The same was observed for ccl9 and cxcl13 in soleus. Also in soleus, ccl2, interleukin (il)6, il1, and cluster of differentiation (cd)68 mRNA levels increased after exercise only in ATF3-KO mice. Endurance training increased the basal mRNA level of hexokinase-2, hormone sensitive lipase, glutathione peroxidase-1, and myosin heavy chain IIa in quadriceps of control mice but not in ATF3-KO mice. In summary, ATF3 attenuates the expression of inflammation-related genes after exercise and thus facilitates molecular adaptation to training.