Shared gene expression profiles in developing heart valves and osteoblast progenitor cells
Shared gene expression profiles in developing heart valves and osteoblast progenitor cells
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DOI：
10.1152/physiolgenomics.90212.2008
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发表时间：
2008-09-01
影响因子：
4.6
通讯作者：
Yutzey, Katherine E.
中科院分区：
文献类型：
--
作者：
Chakraborty, Santanu;Cheek, Jonathan;Yutzey, Katherine E.
Chakraborty S，Cheek J，Sakthivel B，Aronow BJ，Yutzey KE.心脏瓣膜和成骨祖细胞发育中的基因表达谱。Physiol Genomics 35：75-85，2008.首次发表于2008年7月8日; doi：10.1152/physiolgenomics.90212.2008。心脏的房室（AV）瓣膜由未分化的间充质内皮细胞垫发育而来，随后成熟为具有多样化细胞外基质（ECM）的分层瓣膜。由于成熟瓣膜表达与成骨相关的基因，并表现出与疾病相关的钙化，我们假设存在共同的调节途径，在AV瓣膜和骨祖细胞的发育中起作用。为了确定与成骨细胞祖细胞相关的瓣膜发生的基因调控程序，我们对小鼠胚胎日龄（E）12.5 AV内膜垫与E17.5 AV瓣膜（二尖瓣和三尖瓣）和前成骨细胞MC 3 T3-E1（亚克隆4）细胞进行了Affyphin基因表达谱分析。总的来说，MC 3 T3细胞与E17.5瓣膜的相似性显著高于E12.5垫，这支持了瓣膜成熟涉及成骨细胞中也表达的许多基因表达的假设。间充质和成骨细胞前体细胞的几个转录因子特征，包括Twist 1，在E12.5垫中占主导地位。瓣膜成熟的特征在于基质金属蛋白酶及其抑制剂以及复合胶原基因表达的差异调节。在瓣膜形成过程中最高度富集的基因是富含亮氨酸的小蛋白聚糖（SLRP）家族的成员，包括Asprin，一种已知的成骨细胞分化和矿化的负调节因子。总之，这些数据支持在正常瓣膜发育和体内平衡中发育瓣膜和成骨细胞骨前体细胞的共同基因表达谱，在钙化瓣膜疾病中具有潜在功能。
Chakraborty S, Cheek J, Sakthivel B, Aronow BJ, Yutzey KE. Shared gene expression profiles in developing heart valves and osteoblast progenitor cells. Physiol Genomics 35: 75-85, 2008. First published July 8, 2008; doi: 10.1152/physiolgenomics.90212.2008.-The atrioventricular (AV) valves of the heart develop from undifferentiated mesenchymal endocardial cushions, which later mature into stratified valves with diversified extracellular matrix (ECM). Because the mature valves express genes associated with osteogenesis and exhibit disease-associated calcification, we hypothesized the existence of shared regulatory pathways active in developing AV valves and in bone progenitor cells. To define gene regulatory programs of valvulogenesis relative to osteoblast progenitors, we undertook Affymetrix gene expression profiling analysis of murine embryonic day (E)12.5 AV endocardial cushions compared with E17.5 AV valves (mitral and tricuspid) and with preosteoblast MC3T3-E1 (subclone4) cells. Overall, MC3T3 cells were significantly more similar to E17.5 valves than to E12.5 cushions, supporting the hypothesis that valve maturation involves the expression of many genes also expressed in osteoblasts. Several transcription factors characteristic of mesenchymal and osteoblast precursor cells, including Twist1, are predominant in E12.5 cushion. Valve maturation is characterized by differential regulation of matrix metalloproteinases and their inhibitors as well as complex collagen gene expression. Among the most highly enriched genes during valvulogenesis were members of the small leucine-rich proteoglycan (SLRP) family including Asporin, a known negative regulator of osteoblast differentiation and mineralization. Together, these data support shared gene expression profiles of the developing valves and osteoblast bone precursor cells in normal valve development and homeostasis with potential functions in calcific valve disease.