OK/basigin expression on red blood cells varies between blood donors and correlates with binding of recombinant Plasmodium falciparum reticulocyte-binding protein homolog 5
OK/basigin expression on red blood cells varies between blood donors and correlates with binding of recombinant Plasmodium falciparum reticulocyte-binding protein homolog 5
复制标题
红细胞上的 OK/basigin 表达因献血者而异，并与重组恶性疟原虫网织红细胞结合蛋白同源物 5 的结合相关
作者：
Luyi Ye;Fengyong Zhao;Qixiu Yang;Jiamin Zhang;Qin Li;Chen Wang;Zhonghui Guo;Ying Yang;Ziyan Zhu
背景：近年来，研究发现携带OK抗原的basigin（BSG）是恶性疟原虫网织红细胞结合蛋白5（PfRh 5）的受体。BSG-PfRh 5是迄今为止已知的恶性疟原虫侵袭中唯一必需的受体-配体对。研究设计和方法：收集血液样本，检测OK/BSG基因的表达。克隆并表达了PfRh 5的编码区。使用基于酶联免疫吸附测定的红细胞结合试验来测量具有不同OK/BSG表达的红细胞的重组PfRh 5（rPfRh 5）结合。对选定的样本进行BSG基因测序和BSG mRNA定量。通过miRNA测序，筛选出可能靶向BSG基因的候选microRNA（miRNAs）。双荧光素酶报告基因检测和miRNAs在K562细胞中的过表达。OK/BSG的表达水平在献血者之间变化，并且与rPfRh 5结合强烈相关。单核苷酸多态性与OK/BSG表达无关。结论：OK/BSG在红细胞上的表达和调控机制尚未完全阐明，但我们的研究结果提示OK/BSG在红细胞上的表达水平可能与恶性疟原虫的侵袭有关。此外，转录后调节可能在控制OK/BSG表达中起作用。
BACKGROUND:Recently, basigin (BSG), which carries OK antigens on red blood cells (RBCs), was reported to be the receptor of thePlasmodium falciparumreticulocyte‐binding protein homolog 5 (PfRh5). BSG–PfRh5 is the only essential receptor–ligand pair inP. falciparuminvasion that is known to date. However, the kind of OK/BSG polymorphism involved in the selection pressure caused byP. falciparummalaria has not been determined.STUDY DESIGN AND METHODS:Blood samples were collected to detect the expression of OK/BSG. The coding region of PfRh5 was cloned and expressed. Enzyme‐linked immunosorbent assay–based erythrocyte binding assay was used to measure the recombinant PfRh5 (rPfRh5) binding of RBCs with different OK/BSG expressions. Sequencing of theBSGgene and quantification of theBSGmRNA were performed for selected samples. The candidate microRNAs (miRNAs), which might target theBSGgene, were obtained by miRNA sequencing. Dual‐Luciferase reporter assay and overexpression of identified miRNAs were performed in K562 cells.RESULTS:The rPfRh5 was successfully expressed and verified. The OK/BSG expression levels varied among blood donors and were strongly associated with rPfRh5 binding. No single‐nucleotide polymorphism was related to the OK/BSG expression. A potentialBSGregulator, miR‐501‐3p, was identified by miRNA sequencing and Dual‐Luciferase assay, but was not proven to regulate the expression of BSG in K562 cells.CONCLUSION:Although the mechanism of OK/BSG expression and regulation on RBCs has not been fully clarified, our findings suggest that the OK/BSG expression levels on RBCs might be related toP. falciparuminvasion. Moreover, posttranscriptional regulation might play a role in controlling the OK/BSG expression.