Dynamic changes of gene expression profiles during postnatal development of the heart in mice

Dynamic changes of gene expression profiles during postnatal development of the heart in mice
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DOI:
10.1136/hrt.2002.006734
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发表时间:
2004-08-01
期刊:
影响因子:
5.7
通讯作者:
Lee, YT
Lee, YT
中科院分区:
医学1区
文献类型:
--
作者:
Chen, HW;Yu, SL;Lee, YT

文献摘要

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目的:研究小鼠出生后心脏的分化。假设:在出生后心脏发育过程中,通过系统的基因表达分析,可能存在心脏分化的机制或因素。方法:利用基因芯片技术,检测6144个基因在小鼠心脏中的表达,包括出生后0天、7天和14天到成年。结果:芯片分析鉴定出多种与心脏发育相关的基因,涉及细胞周期相关基因(细胞周期蛋白B1、增殖细胞核抗原和Ki67)、生长因子基因(IGF-II、多营养素和中期因子)以及转录调控、细胞骨架和解毒酶等。其中一些基因的RNA和蛋白质含量也通过Northern印迹和免疫组织化学方法得到了证实。体内给予PTN(20 ng/g)可使小鼠心脏组织中溴脱氧尿嘧啶核苷掺入量增加2.24倍,增殖细胞核抗原表达增加1.71倍,提示PTN可诱导小鼠心脏细胞增殖。结论:PTN对小鼠心脏整体基因表达的分析可能有助于了解心脏环境中出生后发育或终末分化的协调过程。这些数据可能有助于研究新生儿心脏发育异常。
Objective: To study postnatal cardiac differentiation in the mouse.Hypothesis: There might be mechanisms or factors in cardiac differentiation that could be identified by systematic gene expression analysis during postnatal cardiac development.Methods: Expression of 6144 genes was examined in mouse heart, from the newborn period (day 0), through day 7 and day 14 day, to adulthood, using the cDNA microarray approach. Northern blotting and immunohistochemical techniques were used to confirm the microarray results.Results: Various cardiac development related genes involving the cell cycle (cyclin B1, proliferating cell nuclear antigen (PCNA), and Ki67), growth factors (IGF-II, pleiotrophin (PTN), and midkine (MK)), and transcriptional regulation, cytoskeleton, and detoxification enzymes were identified by microarray analysis. Some of these genes were also confirmed by Northern blotting and immunohistochemistry of their RNA and protein content. In vivo treatment with PTN (20 ng/g) increased bromodeoxyuridine incorporation (by 2.24-fold) and PCNA expression (by 1.71-fold) during day 7 to day 14, indicating that PTN induces cell proliferation in mouse heart.Conclusions: Global gene expression analysis in the whole heart may be useful in understanding the orchestrated process of postnatal development or terminal differentiation in the cardiac environment. These data are likely to be helpful in studying developmental anomalies of the heart in neonates.