Circulating exosomes may identify biomarkers for cows at risk for metabolic dysfunction
Circulating exosomes may identify biomarkers for cows at risk for metabolic dysfunction
复制标题
DOI：
10.1038/s41598-019-50244-7
复制
发表时间：
2019-09-25
影响因子：
4.6
通讯作者：
Mitchell, Murray D.
中科院分区：
文献类型：
--
作者：
Almughlliq, Fatema B.;Koh, Yong Q.;Mitchell, Murray D.
奶牛从妊娠期到哺乳期的过渡期是疾病易感性最大的时期。循环外泌体可以提供生物标志物来检测风险奶牛，以提高健康和生产力。从490头奶牛中，使用产犊后两周内的血浆非酯化脂肪酸和β-羟基丁酸酯浓度以及肝脏甘油三酯浓度确定了高风险（n = 20）或低风险（n = 20）的过渡相关疾病动物。我们从低风险（LR-EXO）和高风险（HR-EXO）奶牛血浆中分离出循环外泌体，并分析其蛋白质组谱以确定代谢功能障碍的标志物。我们评估了这些外泌体对牛子宫内膜间质（bCSC）和上皮（bEEL）细胞类花生酸途径表达的影响。与LR-EXO相比，HR-EXO具有显著较低的循环外泌体产量，并且在HR-EXO和LR-EXO中鉴定出独特的蛋白质。暴露于LR-EXO或HR-EXO差异调节bCSC和bEEL细胞中类花生酸基因的表达和产生。在bCSC中，LR-EXO暴露增加PGE（2）和PGD（2）的产生，而HR-EXO暴露增加PTGS 2基因表达。在bEEL中，HR-EXO暴露导致PGE（2）、PGF（2 α）、PGD（2）、PGFM和TXB 2产生减少。丝氨酸蛋白酶抑制剂A3-7、含有88 A的卷曲螺旋结构域和HREXO中的丝氨酸蛋白酶抑制剂/激活素β A链的独特存在，表明存在代谢性疾病风险的奶牛的潜在生物标志物。我们的结果与奶牛的健康状况一致，表明外泌体在增强奶牛健康和生育力方面具有潜在的诊断作用。
Disease susceptibility of dairy cows is greatest during the transition from pregnancy to lactation. Circulating exosomes may provide biomarkers to detect at-risk cows to enhance health and productivity. From 490 cows, animals at high-(n = 20) or low-risk (n = 20) of transition-related diseases were identified using plasma non-esterified fatty acid and beta-hydroxybutyrate concentrations and liver triacylglyceride concentrations during the two weeks post-calving. We isolated circulating exosomes from plasma of dairy cows at low-risk (LR-EXO) and high-risk (HR-EXO), and analyzed their proteome profiles to determine markers for metabolic dysfunction. We evaluated the effects of these exosomes on eicosanoid pathway expression by bovine endometrial stromal (bCSC) and epithelial (bEEL) cells. HR-EXO had significantly lower yield of circulating exosomes compared with LR-EXO, and unique proteins were identified in HR-EXO and LR-EXO. Exposure to LR-EXO or HR-EXO differentially regulated eicosanoid gene expression and production in bCSC and bEEL cells. In bCSC, LR-EXO exposure increased PGE(2) and PGD(2) production, whereas HR-EXO exposure increased PTGS2 gene expression. In bEEL, HR-EXO exposure caused a decrease in PGE(2), PGF(2 alpha), PGD(2), PGFM and TXB2 production. The unique presence of serpin A3-7, coiled-coil domain containing 88A and inhibin/ activin beta A chain in HREXO, indicates potential biomarkers for cows at-risk for metabolic diseases. Our results are in line with the health status of the cow indicating a potential diagnostic role for exosomes in enhancing cows' health and fertility.