Edinburgh Research Explorer Gene expression profiling of mammary gland development reveals putative roles for death receptors and immune mediators in post-lactational regression
Edinburgh Research Explorer Gene expression profiling of mammary gland development reveals putative roles for death receptors and immune mediators in post-lactational regression
复制标题
DOI：
--
复制
发表时间：
--
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
引言为了更好地了解乳腺细胞凋亡和组织退化的分子过程，我们进行了大规模的小鼠乳腺妊娠周期中的转录变化分析，重点是从泌乳到退化的过渡。方法采用Affyssin基因芯片技术，对12个时间点（1个处女、3个妊娠、3个哺乳和5个退化期）的乳腺组织进行比较，共包含8618个基因。每个时间点使用6只动物。在所有时间点的基因表达的共同模式进行了鉴定，并与生物功能。结果大多数在退化中显着诱导的基因在妊娠周期的早期阶段也受到差异调节。这包括在退化和分娩过程中炎症介质的显着增加，这与白血病抑制因子-Stat 3（信号转导和信号传导激活剂-3）信号。在退化之前，观察到细胞增殖、生物合成和代谢相关基因的预期增加。在退化过程中，断奶后的第一个24小时的特点是细胞凋亡，炎性细胞因子和急性期反应基因的死亡受体途径的成分的表达短暂增加。24小时后，内在细胞凋亡的调节剂与吞噬细胞活性的标志物、基质蛋白酶、嗜中性粒细胞抑制剂和特异性和先天性免疫的可溶性组分一起诱导。结论提供了一个可供下载或在线分析的小鼠乳腺基因表达数据库。在这里，我们强调的顺序诱导不同的细胞凋亡途径的退化和刺激的免疫调节信号，这可能会抑制潜在的破坏性影响的细胞炎症反应，同时保持适当的抗菌和吞噬环境。
Introduction In order to gain a better understanding of the molecular processes that underlie apoptosis and tissue regression in mammary gland, we undertook a large-scale analysis of transcriptional changes during the mouse mammary pregnancy cycle, with emphasis on the transition from lactation to involution. Method Affymetrix microarrays, representing 8618 genes, were used to compare mammary tissue from 12 time points (one virgin, three gestation, three lactation and five involution stages). Six animals were used for each time point. Common patterns of gene expression across all time points were identified and related to biological function. Results The majority of significantly induced genes in involution were also differentially regulated at earlier stages in the pregnancy cycle. This included a marked increase in inflammatory mediators during involution and at parturition, which correlated with leukaemia inhibitory factor–Stat3 (signal transducer and activator of signalling-3) signalling. Before involution, expected increases in cell proliferation, biosynthesis and metabolism-related genes were observed. During involution, the first 24 hours after weaning was characterized by a transient increase in expression of components of the death receptor pathways of apoptosis, inflammatory cytokines and acute phase response genes. After 24 hours, regulators of intrinsic apoptosis were induced in conjunction with markers of phagocyte activity, matrix proteases, suppressors of neutrophils and soluble components of specific and innate immunity. Conclusion We provide a resource of mouse mammary gene expression data for download or online analysis. Here we highlight the sequential induction of distinct apoptosis pathways in involution and the stimulation of immunomodulatory signals, which probably suppress the potentially damaging effects of a cellular inflammatory response while maintaining an appropriate antimicrobial and phagocytic environment.