Microarray analysis of bladder smooth muscle from patients with myelomeningocele
Microarray analysis of bladder smooth muscle from patients with myelomeningocele
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DOI：
10.1111/j.1464-410x.2008.07606.x
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发表时间：
2008-09-01
影响因子：
4.5
通讯作者：
Andersson, Karl-Erik
中科院分区：
文献类型：
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作者：
Hipp, Jennifer A.;Hipp, Jason D.;Andersson, Karl-Erik
为了验证基因谱能否为脊髓脊膜脑膨出(MM)患者的质量和治疗潜力提供分子评估，通过比较来自患者的健康膀胱和膀胱的平滑肌细胞(SMC)的基因谱，确定MM膀胱SMC中过度和低表达的基因。从接受膀胱输尿管返流手术的健康患者和继发于MM的神经源性膀胱的患者获得BLIDA SM活组织标本。用两种方法鉴定差异表达基因。在第一个分析中，我们直接比较了健康SMC和MM患者的原始数据集。在第二个分析中，我们间接将健康SMC和MM SMC与参考文件进行比较，以创建MM SMC中过度表达和低表达的基因的基因签名。直接分析确定了240个在MM SMC中过度表达的基因和104个低表达基因。基因本体论分类用于确定生物学主题和途径。在MM SMCs中过表达的基因有：间充质同源盒2(翻倍变化，9.3)；骨形态发生蛋白6(4.0)；成纤维细胞生长因子2(4.8)；抑制素A(4.2)，软骨脂肪基质蛋白(9.97)；11A胶原(6)；5A2胶原(3)和1A1胶原(2.18)。间接分析确定了665个基因在MM SMC中过度表达，1343个基因在MM SMC中低表达。对这些遗传信号的基于途径的分析表明，与肌肉发育和局部粘连/细胞外基质相互作用有关的基因过度表达。MM SMC中低表达的基因被映射到肌肉收缩、神经冲动传递和细胞-细胞黏附途径。我们的结果与先前的研究一致，表明MM膀胱有过量的细胞外基质沉积，不适当的收缩，并且相对于健康的SMC发育不成熟。基因芯片分析MM SMCs的临床意义在于它提供了诱导肌肉分化和抑制细胞外基质产生的潜在靶点。
To examine whether gene profiles can provide a molecular evaluation of the quality and therapeutic potential in patients with myelomeningocele (MM), by comparing genetic profiles of smooth muscle cells (SMCs) from healthy bladders and bladders from patients, to identify genes that are over- and under-expressed in MM bladder SMCs.Bladder SM biopsies were obtained from 'healthy' subjects undergoing bladder surgery for vesico-ureteric reflux and from patients with a neurogenic bladder secondary to MM. Bladder SMCs were expanded in vitro and total RNA was isolated and hybridized to gene chips to evaluate the differential expression levels of 22 283 genes. Differentially expressed genes were identified by two methods. In the first analysis, we directly compared raw data sets of healthy SMCs to those derived from patients with MM. In the second analysis, we indirectly compared healthy SMCs and MM SMCs to a reference file, to create a genetic signature of genes that are over- and under-expressed in MM SMCs.The direct analysis identified 240 genes that were over-expressed and 104 that were under-expressed in MM SMCs. Gene ontology classifications were used to identify biological themes and pathways. Genes that were over-expressed in MM SMCs were involved in development: mesenchyme homeobox 2 (-fold change, 9.3); bone morphogenic protein 6 (4.0); fibroblast growth factor 2 (4.8); inhibin A (4.2), cartilage oliogomeric matrix protein (9.97); collagen 11A (6); collagen 5A2 (3) and collagen 1A1 (2.18). The indirect analysis identified 665 genes that were over-expressed and 1343 that were under-expressed in MM SMCs. Pathway-based analysis of these genetic signatures showed an over-expression of genes involved in muscle development and focal adhesion/extracellular matrix interactions. Genes that were under-expressed in MM SMCs were mapped to muscle contraction, transmission of nerve impulses, and cell-cell adhesion pathways.Our results are consistent with previous studies showing that MM bladders have an excess of extracellular matrix deposition, improper contraction, and are developmentally immature relatively to healthy SMCs. The clinical implication of microarray analysis of MM SMCs is that it provides potential targets that could induce muscle differentiation and inhibit extracellular matrix production.