Donor Graft MicroRNAs: A Newly Identified Player in the Development of New-onset Diabetes After Liver Transplantation.
Donor Graft MicroRNAs: A Newly Identified Player in the Development of New-onset Diabetes After Liver Transplantation.
复制标题
供体移植 MicroRNA：肝移植后新发糖尿病发展中新发现的参与者。
DOI：
10.1111/ajt.13984
复制
发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Zheng S
中科院分区：
文献类型：
--
作者：
Ling Q;Xie H;Li J;Liu J;Cao J;Yang F;Wang C;Hu Q;Xu X;Zheng S
肝移植术后新发糖尿病（NODALT）是一种常见的并发症，结局不利。我们以前证明了供体移植物遗传学和NODALT风险之间的重要联系。我们使用倾向评分匹配分析选择了15对匹配的NODALT和非NODALT肝脏受体。检测供体肝组织中10种调节人肝葡萄糖稳态的microRNA（miRNAs）的表达。利用基因本体论和京都基因与基因组百科全书（KEGG）富集分析预测潜在靶基因的生物学功能。与非NODALT组相比，NODALT组中miR-103和miR-181 a均显著高表达。预测的靶基因（例如Irs 2、Pik 3r 1、Akt 2和Gsk 3b）参与葡萄糖输入和胰岛素信号通路。我们还观察到用他克莫司或高糖处理的培养人肝细胞中的miRNA（例如let-7，miR-26 b，miR-145和miR-183）失调，这是该队列中确定的NODALT的两个独立风险因素。富集分析显示，他克莫司或高血糖改变的肝脏miRNA谱与胰岛素抵抗和葡萄糖稳态失衡相关。疾病易感性miRNA表达模式可直接从供体导入，并通过移植因素得到巩固。最初控制肝脏葡萄糖稳态的供体移植物microRNA可能受到移植因素（如早期高血糖症和免疫抑制药物）的影响，随后可能导致肝移植受者新发糖尿病的发生。
New‐onset diabetes after liver transplantation (NODALT) is a frequent complication with an unfavorable outcome. We previously demonstrated a crucial link between donor graft genetics and the risk of NODALT. We selected 15 matched pairs of NODALT and non‐NODALT liver recipients using propensity score matching analysis. The donor liver tissues were tested for the expression of 10 microRNAs (miRNAs) regulating human hepatic glucose homeostasis. The biological functions of potential target genes were predicted using gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Both miR‐103 and miR‐181a were significantly highly expressed in the NODALT group as compared to the non‐NODALT group. The predicted target genes (e.g. Irs2, Pik3r1, Akt2, and Gsk3b) were involved in glucose import and the insulin signaling pathway. We also observed dysregulation of miRNAs (e.g. let‐7, miR‐26b, miR‐145, and miR‐183) in cultured human hepatocytes treated with tacrolimus or high glucose, the two independent risk factors of NODALT identified in this cohort. The hepatic miRNA profiles altered by tacrolimus or hyperglycemia were associated with insulin resistance and glucose homeostatic imbalance as revealed by enrichment analysis. The disease susceptibility miRNA expressive pattern could be imported directly from the donor and consolidated by the transplant factors. Donor graft microRNAs, initially controlling hepatic glucose homeostasis, could be affected by transplant factors such as early hyperglycemia and immunosuppressive drugs, and could subsequently contribute to the development of new‐onset diabetes in liver transplant recipients.
登录
查看更多内容
影响因子：
4.4
作者：
Kwekel JC;Desai VG;Moland CL;Branham WS;Fuscoe JC
通讯作者：
Fuscoe JC
肝移植后新发糖尿病的根源：肝脏、胰岛还是肠道？
影响因子：
6.2
作者：
Ling, Qi;Xu, Xiao;Zheng, Shusen
通讯作者：
Zheng, Shusen
影响因子：
0.9
作者：
Lankarani, Kamran Bagheri;Eshraghian, Ahad;Malek-Hosseini, Seyed Ali
通讯作者：
Malek-Hosseini, Seyed Ali
影响因子：
4.3
作者：
Kawahito, Shinji;Kitahata, Hiroshi;Oshita, Shuzo
通讯作者：
Oshita, Shuzo
影响因子：
4.6
作者：
Farid, Waqar R. R.;Pan, Qiuwei;van der Laan, Luc J. W.
通讯作者：
van der Laan, Luc J. W.