表观遗传机制有助于在采食高浓缩日粮的奶牛肝脏中免疫相关基因的表达。
Epigenetic mechanisms contribute to the expression of immune related genes in the livers of dairy cows fed a high concentrate diet.
作者信息
Chang Guangjun, Zhang Kai, Xu Tianle, Jin Di, Guo Junfei, Zhuang Su, Shen Xiangzhen
机构信息
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, P. R. China.
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, P. R. China.
出版信息
PLoS One. 2015 Apr 10;10(4):e0123942. doi: 10.1371/journal.pone.0123942. eCollection 2015.
PURPOSE
Epigenetic modifications critically regulate the expression of immune-related genes in response to inflammatory stimuli. It has been extensively reported that a high concentrate (HC) diet can trigger systemic inflammation in dairy cows, yet it is unclear whether epigenetic regulation is involved in the expression of immune genes in the livers of dairy cows. This study aimed to investigate the impact of epigenetic modifications on the expression of immune-related genes.
EXPERIMENTAL DESIGN
In eight mid-lactating cows, we installed a rumen cannula and catheters of the portal and hepatic veins. Cows were randomly assigned to either the treatment group fed a high concentrate (HC) diet (60% concentrate + 40% forage, n = 4) or a control group fed a low concentrate (LC) diet (40% concentrate + 60% forage, n = 4).
RESULTS
After 10 weeks of feeding, the rumen pH was reduced, and levels of lipopolysaccharide (LPS) in the rumen, and portal and hepatic veins were notably increased in the HC group compared with the LC group. The expression levels of detected immune response-related genes, including Toll-like receptor 4 (TLR4), cytokines, chemokines, and acute phase proteins, were significantly up-regulated in the livers of cows fed a HC diet. Chromatin loosening at the promoter region of four candidate immune-related genes (TLR4, LPS-binding protein, haptoglobin, and serum amyloid A3) was elicited, and was strongly correlated with enhanced expression of these genes in the HC group. Demethylation at the promoter region of all four candidate immune-related genes was accompanied by chromatin decompaction.
CONCLUSION
After HC diet feeding, LPS derived from the digestive tract translocated to the liver via the portal vein, enhancing hepatic immune gene expression. The up-regulation of these immune genes was mediated by epigenetic mechanisms, which involve chromatin remodeling and DNA methylation. Our findings suggest that modulating epigenetic mechanisms could provide novel ways to treat systemic inflammatory responses elicited by the feeding of a HC diet.
目的
表观遗传修饰在响应炎症刺激时对免疫相关基因的表达起着关键调节作用。已有大量报道称，高浓缩物（HC）日粮会引发奶牛的全身炎症，但尚不清楚表观遗传调控是否参与奶牛肝脏中免疫基因的表达。本研究旨在探讨表观遗传修饰对免疫相关基因表达的影响。
实验设计
在八头处于泌乳中期的奶牛中，安装瘤胃瘘管以及门静脉和肝静脉导管。奶牛被随机分为两组，一组为喂食高浓缩物（HC）日粮（60%浓缩物 + 40%草料，n = 4）的处理组，另一组为喂食低浓缩物（LC）日粮（40%浓缩物 + 60%草料，n = 4）的对照组。
结果
经过10周的喂养后，HC组的瘤胃pH值降低，瘤胃、门静脉和肝静脉中的脂多糖（LPS）水平与LC组相比显著升高。在喂食HC日粮的奶牛肝脏中，包括Toll样受体4（TLR4）、细胞因子、趋化因子和急性期蛋白在内的检测到的免疫反应相关基因的表达水平显著上调。引发了四个候选免疫相关基因（TLR4、LPS结合蛋白、触珠蛋白和血清淀粉样蛋白A3）启动子区域的染色质松弛，并且与HC组中这些基因表达的增强密切相关。所有四个候选免疫相关基因启动子区域的去甲基化伴随着染色质解压缩。
结论
喂食HC日粮后，来自消化道的LPS通过门静脉转移至肝脏，增强了肝脏免疫基因的表达。这些免疫基因的上调是由表观遗传机制介导的，该机制涉及染色质重塑和DNA甲基化。我们的研究结果表明，调节表观遗传机制可为治疗由喂食HC日粮引发的全身炎症反应提供新方法。
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