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Onset of lactation in the bovine mammary gland: gene expression profiling indicates a strong inhibition of gene expression in cell proliferation

机译:牛乳腺泌乳期开始:基因表达谱表明细胞增殖中基因表达受到强烈抑制

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摘要

The mammary gland undergoes dramatic functional and metabolic changes during the transition from late pregnancy to lactation. To better understand the molecular events underlying these changes, we analyzed expression profiles of approximately 23,000 gene transcripts in bovine mammary tissue about day 5 before parturition and day 10 after parturition. At the cutoff criteria of the signed fold change ≥2 or ≤?2 and false discovery rate (FDR) ≤0.1, a total of 389 transcripts (1.6%) were significantly differentially expressed at the two stages. Of these transcripts with significant changes, 105 were up-regulated while 284 were down-regulated. Gene ontology analysis showed that the main up-regulated genes were those associated with transport activity (amino acid, glucose, and ion transporters), lipid and carbohydrate metabolism (lipoprotein lipase, acetyl-Coenzyme A synthetases, 6-phosphofructo-2-kinase, etc.), and cell signaling factors (protein p8, Rab18, etc.). The main down-regulated genes were associated with cell cycle and proliferation (cyclins, cell division cycle associated proteins, etc.), DNA replication and chromosome organization (centromere proteins, minichromosome maintenance proteins, histone, etc.), microtubule-based processes (microtubule associated protein tau, kinesin, tubulins, etc.), and protein and RNA degradation (proteasome, proteasome activator, RNA binding motif protein, etc.). The increased expression of glucose transporter GLUT1 mRNA during lactation was verified by quantitative reverse transcription/polymerase chain reactin (PCR) (P < 0.05). GLUT1 protein also increased twofold during lactation (P < 0.05). Furthermore, GLUT1 protein was primarily localized in mammary ductal epithelia and blood vessel endothelia before parturition, but was predominantly localized in the basolateral and apical membranes of mammary alveolar epithelial cells during lactation. Our microarray data provide insight into the molecular events in the mammary gland at the onset of lactation, indicating the up-regulation of genes involved in milk synthesis concomitant with the inhibition of those related to cell proliferation.
机译:从妊娠晚期到哺乳期,乳腺发生巨大的功能和代谢变化。为了更好地理解这些变化背后的分子事件,我们分析了分娩前第5天和分娩后第10天,牛乳腺组织中约23,000个基因转录物的表达谱。在有符号倍数变化≥2或≤?2和错误发现率(FDR)≤0.1的截止标准下,两个阶段共有389个转录本(1.6%)显着差异表达。在这些有显着变化的成绩单中,有105个上调而有284个下调。基因本体分析显示,主要上调的基因是与运输活性(氨基酸,葡萄糖和离子转运蛋白),脂质和碳水化合物代谢(脂蛋白脂肪酶,乙酰辅酶A合成酶,6-磷酸果糖-2-激酶,等)和细胞信号传导因子(蛋白p8,Rab18等)。主要下调的基因与细胞周期和增殖(细胞周期蛋白,细胞分裂周期相关蛋白等),DNA复制和染色体组织(着丝粒蛋白,微染色体维持蛋白,组蛋白等),基于微管的过程(微管相关蛋白tau,驱动蛋白,微管蛋白等,以及蛋白和RNA降解(蛋白酶体,蛋白酶体激活剂,RNA结合基序蛋白等)。通过定量逆转录/聚合酶链反应(PCR)验证了泌乳期葡萄糖转运蛋白GLUT1 mRNA的表达增加(P <0.05)。泌乳期间GLUT1蛋白也增加了两倍(P <0.05)。此外,GLUT1蛋白在分娩前主要位于乳腺导管上皮和血管内皮中,但在泌乳期间主要位于乳腺肺泡上皮细胞的基底外侧和顶膜中。我们的微阵列数据提供了对泌乳开始时乳腺中分子事件的深入了解,表明与牛奶合成相关的基因的上调与对与细胞增殖相关的基因的抑制相伴随。

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