Wang Na, Qin Xiaoyi, Cao Yigeng, Liang Bin, Yu Kang, Ye Haige
Wenzhou Medical University, Wenzhou, Zhejiang 325002 China.
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020 China.
J Inflamm (Lond). 2018 Jan 5;15:1. doi: 10.1186/s12950-017-0178-z. eCollection 2018.
Gastrointestinal acute graft-versus-host disease (GI aGVHD) is a lethal complication following allogeneic hematopoietic stem cell transplantation (HSCT). However, it is still very difficult to make a diagnosis of GI aGVHD in practice. To date, no consensus plasma biomarker of GI aGVHD can be used to help make a diagnosis. Here, we attempted to identify GI aGVHD associated plasma proteins in murine model, which can help make a diagnosis of GI aGVHD.
We used 8-plex isobaric tags for relative and absolute quantitation (8-plex iTRAQ) to screen out proteins in plasma samples taken from murine models before and after allogeneic HSCT. Next mRNA expressions were validated by quantitative real-time polymerase chain reaction in mouse intestinal epithelial samples.
We found that five proteins were increased at least 2-fold in the allogeneic group at day 7 compared with days 0, 3 and 15 (after Cyclosporin A treatment) and the syngeneic group at day 7. These 5 proteins were VNN3, ZNF746, C4BP, KNG1 and FETUB, and they were consistent with results from negative labeling with 8-plex iTRAQ. Furthermore, increase in mRNA level of VNN3 was confirmed in murine intestinal epithelial samples with aGVHD.
Our results demonstrate that plasma VNN3 protein is associated with GI aGVHD in murine model.
胃肠道急性移植物抗宿主病(GI aGVHD)是异基因造血干细胞移植(HSCT)后的一种致命并发症。然而,在实际中对GI aGVHD进行诊断仍然非常困难。迄今为止,尚无用于帮助诊断的GI aGVHD共识血浆生物标志物。在此,我们试图在小鼠模型中鉴定与GI aGVHD相关的血浆蛋白,以帮助诊断GI aGVHD。
我们使用8重等压标签相对和绝对定量(8重iTRAQ)来筛选异基因HSCT前后从小鼠模型采集的血浆样本中的蛋白质。接下来,通过定量实时聚合酶链反应在小鼠肠上皮样本中验证mRNA表达。
我们发现,与第0、3和15天(环孢素A治疗后)的同基因组以及第7天的同基因组相比,异基因组在第7天有5种蛋白质增加了至少2倍。这5种蛋白质是VNN3、ZNF746、C4BP、KNG1和FETUB,它们与8重iTRAQ阴性标记的结果一致。此外,在患有aGVHD的小鼠肠上皮样本中证实了VNN3的mRNA水平升高。
我们的结果表明,血浆VNN3蛋白与小鼠模型中的GI aGVHD相关。