MicroRNA-122 ameliorates corneal allograft rejection through the downregulation of its target CPEB1.
MicroRNA-122 ameliorates corneal allograft rejection through the downregulation of its target CPEB1.
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MicroRNA-122 通过下调其靶标 CPEB1 改善角膜同种异体移植排斥
DOI：
10.1038/cddiscovery.2017.21
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发表时间：
2017
影响因子：
7
通讯作者：
Shi W
中科院分区：
文献类型：
--
作者：
Wang T;Li F;Geng W;Ruan Q;Shi W
排斥反应是角膜移植失败的主要原因。MicroRNA（miRNAs）是一类以序列特异性方式调控基因表达的小分子RNA家族。近年来研究表明，miRNAs在人类器官移植中发挥重要作用，但与角膜移植排斥反应直接相关的miRNAs的报道仍然有限。为了研究miRNAs在角膜移植排斥反应中的作用，我们建立了小鼠穿透性角膜移植模型，并使用微阵列筛选差异表达的miRNAs。我们的结果显示，在同种异体组中，miR-122的表达显著降低。与此结果一致，细胞质多聚腺苷酸化元件结合蛋白-1（CPEB 1）（miR-122的直接靶点）的表达显著增加。进一步的分析表明，miR-122通过下调其靶点CPEB 1抑制炎症性角膜基质细胞凋亡。我们还发现，增加miR-122表达显著降低了角膜移植排斥反应的风险。因此，我们的研究结果表明，miR-122是与角膜移植排斥反应相关的重要miRNA，可用作预防角膜移植术后免疫排斥反应的治疗靶点。
Transplant rejection is a major cause of corneal transplantation failure. MicroRNAs (miRNAs) are a family of small RNAs that regulates gene expression in a sequence-specific manner. miRNAs have recently been shown to have important roles in human organ transplantation, but reports of miRNAs directly associated with corneal transplantation rejection remain limited. To investigate the role of miRNAs during corneal allograft rejection, we established a mouse penetrating keratoplasty model and used microarrays to screen for differentially expressed miRNAs. Our results revealed that the expression of miR-122 was significantly decreased in the allogeneic group. Consistent with this result, the expression of cytoplasmic polyadenylation element-binding protein-1 (CPEB1), a direct target of miR-122, was significantly increased. Further analysis demonstrated that miR-122 inhibited inflammatory cytokine-induced apoptosis in corneal keratocytes through the downregulation of its target CPEB1. We also found that increased miR-122 expression significantly reduced the risk of corneal transplantation rejection. Thus, our results indicate that miR-122 is an important miRNA associated with corneal graft rejection and can be used as a therapeutic target for the prevention of immune rejection after keratoplasty.