A novel evaluation method of survival motor neuron protein as a biomarker of spinal muscular atrophy by imaging flow cytometry
A novel evaluation method of survival motor neuron protein as a biomarker of spinal muscular atrophy by imaging flow cytometry
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DOI：
10.1016/j.bbrc.2014.09.087
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发表时间：
2014-10-24
影响因子：
3.1
通讯作者：
Nomoto, Akio
中科院分区：
文献类型：
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作者：
Arakawa, Masayuki;Arakawa, Reiko;Nomoto, Akio
脊髓性肌萎缩症（SMA）是由存活运动神经元1 （SMN1）基因突变引起的。这些突变导致脊髓运动神经元和其他组织中存活运动神经元（SMN）蛋白表达和SMN复合物的减少。在最近的SMA临床研究中，使用酶联免疫吸附试验（ELISA）将SMN蛋白用作治疗性生物标志物。在这里，我们研究了成像流式细胞术是否可以作为SMN蛋白定量信息的可行来源。使用FlowSight成像流式细胞仪（Merck-Millipore，德国），我们证明成像流式细胞仪可以成功识别健康人成纤维细胞和SMA患者来源的成纤维细胞中SMN蛋白的不同表达模式和亚细胞定位。此外，我们还可以在体外评价丙戊酸对SMA患者源性细胞SMN蛋白表达的治疗效果。因此，我们认为成像流式细胞术技术有潜力识别SMN蛋白的表达水平和模式，作为临床研究的评估工具。(C) 2014爱思唯尔公司版权所有。
Spinal muscular atrophy (SMA) is caused by mutations within the survival motor neuron 1 (SMN1) gene. These mutations result in the reduction of survival motor neuron (SMN) protein expression and SMN complex in spinal motor neurons and other tissues. SMN protein has been used as a therapeutic biomarker in recent SMA clinical studies using enzyme-linked immunosorbent assay (ELISA). Here, we investigated whether imaging flow cytometry can be a viable source of quantitative information on the SMN protein. Using a FlowSight imaging flow cytometer (Merck-Millipore, Germany), we demonstrated that imaging flow cytometry could successfully identify different expression patterns and subcellular localization of SMN protein in healthy human fibroblasts and SMA patient-derived fibroblasts. In addition, we could also evaluate the therapeutic effects of SMN protein expression by valproic acid treatment of SMA patient-derived cells in vitro. Therefore, we suggest that imaging flow cytometry technology has the potential for identifying SMN protein expression level and pattern as an evaluation tool of clinical studies. (C) 2014 Elsevier Inc. All rights reserved.