Pre-B-cell colony-enhancing factor as a potential novel biomarker in acute lung injury
Pre-B-cell colony-enhancing factor as a potential novel biomarker in acute lung injury
复制标题
DOI：
10.1164/rccm.200404-563oc
复制
发表时间：
2005-02-15
影响因子：
24.7
通讯作者：
Garcia, JGN
中科院分区：
文献类型：
--
作者：
Ye, SQ;Simon, BA;Garcia, JGN
虽然急性肺损伤（ALI）的致病和遗传基础仍不完全清楚，新的ALI生物标志物的鉴定有希望获得独特的见解。在ALI动物模型（犬和鼠）和人ALI中的表达谱检测到前B细胞集落增强因子（PBEF）的显著表达，这是一种以前与肺病理生理学无关的基因。这些结果得到了验证，实时聚合酶链反应和免疫组化研究，PBEF蛋白水平显着增加，支气管肺泡灌洗液和血清中的ALI模型和细胞因子或循环拉伸激活的肺微血管内皮细胞。我们在一个特征良好的样本中对两个PBEF单核苷酸多态性（SNP）进行了基因分型，这些样本包括脓毒症相关性ALI的白色患者、严重脓毒症患者和健康受试者，并观察到来自SNP T-1001 G和C-1543 T的单倍型GC携带者发生ALI的风险高7.7倍（95%置信区间3.01-19.75，p < 0.001）。通过报告基因测定，来自SNP C-1543 T的T变体导致转录率显著降低（1.8倍; p < 0.01）。总之，这些结果有力地表明PBEF是ALI中潜在的新型生物标志物，并证明了稳健的基因组技术在复杂肺部疾病候选基因鉴定中的成功应用。
Although the pathogenic and genetic basis of acute lung injury (ALI) remains incompletely understood, the identification of novel ALI biomarkers holds promise for unique insights. Expression profiling in animal models of ALI (canine and murine) and human ALI detected significant expression of pre-B-cell colony-enhancing factor (PBEF), a gene not previously associated with lung pathophysiology. These results were validated by real-time polymerase chain reaction and immunohistochemistry studies, with PBEF protein levels significantly increased in both bronchoalveolar lavage fluid and serum of ALI models and in cytokine- or cyclic stretch-activated lung microvascular endothelium. We genotyped two PBEF single-nucleotide polymorphisms (SNPs) in a well characterized sample of white patients with sepsis-associated ALI, patients with severe sepsis, and healthy subjects and observed that carriers of the haplotype GC from SNPs T-1001G and C-1543T had a 7.7-fold higher risk of ALI (95% confidence interval 3.01-19.75, p < 0.001). The T variant from the SNP C-1543T resulted in a significant decrease in the transcription rate (1.8-fold; p < 0.01) by the reporter gene assay. Together, these results strongly indicate that PBEF is a potential novel biomarker in ALI and demonstrate the successful application of robust genomic technologies in the identification of candidate genes in complex lung disease.