Multi-omics integrative analysis revealed characteristic changes in blood cell immunity and amino acid metabolism in a silkworm model of hyperproteinemia
Multi-omics integrative analysis revealed characteristic changes in blood cell immunity and amino acid metabolism in a silkworm model of hyperproteinemia
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DOI：
10.1016/j.ijbiomac.2023.128809
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发表时间：
2023-12-22
影响因子：
8.2
通讯作者：
Xu，Shiqing
中科院分区：
文献类型：
--
作者：
Wang，Guang;Jiang，Guihua;Xu，Shiqing
高蛋白血症是人类和动物的一种严重的代谢性疾病，其特征在于异常高的血浆蛋白浓度（HPPC）。虽然高蛋白血症可导致血细胞稳态失衡，但血细胞的功能变化仍不清楚。在此，使用HPPC蚕模型来评估与血细胞代谢和免疫功能相关的基因的染色质可及性和转录水平的变化。结果表明，HPPC增强了血细胞的吞噬作用，增加了细胞吞噬、增殖、应激和程序性死亡相关基因的染色质可及性和转录水平，同时抑制了血细胞中与芳香族氨基酸代谢和抗菌肽合成相关的基因。对启动子区的染色质可及性的进一步分析发现，对HPPC敏感的基因的高染色质可及性与组蛋白修饰有关，包括组蛋白H3的赖氨酸残基4的三甲基化和组蛋白H3的赖氨酸残基27的乙酰化。HPPC家蚕模型血细胞中免疫功能和氨基酸代谢相关基因的染色质可及性和转录水平的变化为进一步研究高蛋白血症介导的表观基因组调控机制提供了有用的参考。
Hyperproteinemia is a serious metabolic disease of both humans and animals characterized by an abnormally high plasma protein concentration (HPPC). Although hyperproteinemia can cause an imbalance in blood cell homeostasis, the functional changes to blood cells remain unclear. Here, a HPPC silkworm model was used to assess changes to the chromatin accessibility and transcript levels of genes related to blood cell metabolism and immune function. The results showed that HPPC enhanced phagocytosis of blood cells, increased chromatin accessibility and transcript levels of genes involved in cell phagocytosis, proliferation, stress, and programmed death, while genes associated with aromatic amino acid metabolism, and antibacterial peptide synthesis were inhibited in blood cells. Further analysis of the chromatin accessibility of the promoter region found that the high chromatin accessibility of genes sensitive to HPPC, was related to histone modifications, including tri-methylation of lysine residue 4 of histone H3 and acetylation of lysine residue 27 of histone H3. Changes to the chromatin accessibility and transcript levels of genes related to immune function and amino acid metabolism in the blood cells of the HPPC silkworm model provided useful references for future studies of the mechanisms underlying epigenomic regulation mediated by hyperproteinemia.