Department of Urology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China.
Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
Biomed Res Int. 2019 Jun 12;2019:1759697. doi: 10.1155/2019/1759697. eCollection 2019.
Delayed graft function (DGF) is one of the major obstacles for graft survival for kidney recipients. It is profound to reduce the incidence of DGF for maintaining long-term graft survival. However, the molecular regulation of DGF is still not adequately explained and the biomarkers for DGF are limited. Exosomes are cell-derived membrane vesicles, contents of which are stable and could be delivered into recipient cells to exert their biological functions. Consequently, exosome-derived proteomic and RNA signature profiles are often used to account for the molecular regulation of diseases or reflect the conditional state of their tissue as biomarkers. Few researches have been done to demonstrate the function of exosomes associated with DGF. In this study, high-throughput sequencing was used to explore the miRNA expression profiling of exosomes in the peripheral blood of kidney recipients with DGF. We identified 52 known and 5 conserved exosomal miRNAs specifically expressed in recipients with DGF. Three coexpressed miRNAs, hsa-miR-33a-5p_R-1, hsa-miR-98-5p, and hsa-miR-151a-5p, were observed to be significantly upregulated in kidney recipients with DGF. Moreover, hsa-miR-151a-5p was positively correlated with the first-week serum CR, BUN, and UA levels of the kidney recipients after transplantation. Furthermore, we also analyzed functions and signaling pathways of the three upregulated miRNAs target genes to uncover putative mechanism of how these exosomal miRNAs functioned in DGF. Overall, these findings identified biomarker candidates for DGF and provided new insights into the important role of the exosomal miRNAs regulation in DGF.
延迟移植物功能(DGF)是肾移植受者移植物存活的主要障碍之一。减少 DGF 的发生率对于维持长期移植物存活至关重要。然而,DGF 的分子调控仍未得到充分解释,且 DGF 的生物标志物有限。外泌体是细胞来源的膜囊泡,其内容物稳定,可以传递到受体细胞中发挥其生物学功能。因此,外泌体衍生的蛋白质组学和 RNA 特征谱常被用于解释疾病的分子调控或反映其组织的条件状态作为生物标志物。目前,很少有研究表明与 DGF 相关的外泌体的功能。在这项研究中,我们使用高通量测序技术来探索 DGF 肾移植受者外周血中外泌体的 miRNA 表达谱。我们鉴定了 52 个已知和 5 个保守的外泌体 miRNA,这些 miRNA 在 DGF 受者中特异性表达。观察到三个共表达的 miRNA,hsa-miR-33a-5p_R-1、hsa-miR-98-5p 和 hsa-miR-151a-5p,在 DGF 肾移植受者中显著上调。此外,hsa-miR-151a-5p 与移植后肾受者第 1 周血清 CR、BUN 和 UA 水平呈正相关。此外,我们还分析了这三个上调的 miRNA 靶基因的功能和信号通路,以揭示这些外泌体 miRNA 在 DGF 中发挥作用的潜在机制。总之,这些发现确定了 DGF 的生物标志物候选物,并为外泌体 miRNA 调控在 DGF 中的重要作用提供了新的见解。
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