Epigenetic mechanisms contribute to the expression of immune related genes in the livers of dairy cows fed a high concentrate diet.
Epigenetic mechanisms contribute to the expression of immune related genes in the livers of dairy cows fed a high concentrate diet.
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表观遗传机制有助于高浓缩日粮奶牛肝脏中免疫相关基因的表达
DOI：
10.1371/journal.pone.0123942
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Shen X
中科院分区：
文献类型：
--
作者：
Chang G;Zhang K;Xu T;Jin D;Guo J;Zhuang S;Shen X
表观遗传修饰在炎症刺激时对免疫相关基因的表达起关键性调节作用。大量研究表明，高浓缩饲料（HC）可引起奶牛全身性炎症，但表观遗传调控是否参与奶牛肝脏免疫基因的表达尚不清楚。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。在8个泌乳中期的奶牛，我们安装了瘤胃插管和导管的门静脉和肝静脉。将奶牛随机分配至饲喂高浓缩物（HC）饲料（60%浓缩物+40%饲料，n = 4）的处理组或饲喂低浓缩物（LC）饲料（40%浓缩物+60%饲料，n = 4）的对照组。饲喂10周后，与LC组相比，HC组瘤胃pH值降低，瘤胃、门静脉和肝静脉中脂多糖（LPS）水平显著升高。检测到的免疫应答相关基因的表达水平，包括Toll样受体4（TLR4），细胞因子，趋化因子和急性期蛋白，显着上调饲喂HC饮食的奶牛的肝脏。在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）的启动子区域的染色质松动被引发，并与HC组中这些基因的表达增强密切相关。所有四个候选免疫相关基因的启动子区域的去甲基化伴随着染色质解压缩。HC饲料喂养后，消化道来源的LPS通过门静脉转位至肝脏，增强肝脏免疫基因表达。这些免疫基因的上调是由表观遗传机制介导的，包括染色质重塑和DNA甲基化。我们的研究结果表明，调节表观遗传机制可以提供新的方法来治疗由HC饮食引起的全身炎症反应。
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. 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). 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. 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.
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