评估MicroRNA375作为临床胰岛移植中移植物损伤的新型生物标志物

Evaluation of MicroRNA375 as a Novel Biomarker for Graft Damage in Clinical Islet Transplantation.

作者信息

Kanak Mazhar A, Takita Morihito, Shahbazov Rauf, Lawrence Michael C, Chung Wen Yuan, Dennison Ashley R, Levy Marlon F, Naziruddin Bashoo

机构信息

1 Institute of Biomedical Studies, Baylor University, Waco, TX. 2 Islet Cell Laboratory, Baylor Research Institute, Dallas, TX. 3 Department of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester, Leicester, UK. 4 Baylor Annette C. and Harold C. Simmons Transplant Institute, Dallas, TX.

出版信息

Transplantation. 2015 Aug;99(8):1568-73. doi: 10.1097/TP.0000000000000625.

DOI:10.1097/TP.0000000000000625

PMID:25769078

Abstract

BACKGROUND

Early and sensitive detection of islet graft damage is essential for improving posttransplant outcomes. MicroRNA 375 (miR375) has been reported as a biomarker of pancreatic β-cell death in small animal models.

METHODS

The miR375 levels were measured in purified human islets, sera from patients with autologous and allogeneic islet transplantation as well as total pancreatectomy alone (nontransplanted group). The miR375 levels were also determined in a miniaturized in vitro tube model comprising human islets and autologous blood.

RESULTS

The miR375 expression level in islets was dose-dependent (P < 0.001) and significantly elevated after islet damage in plasma in the in vitro model (P = 0.003). Clinical analysis revealed that circulating miR375 levels in both autologous and allogeneic islet recipients were significantly elevated for 7 days after islet infusion, compared with the nontransplanted group (P = 0.005 and <0.001, respectively). Furthermore, miR375 detected the difference in islet graft damage among 3 different anti-inflammatory protocols for clinical autologous transplantation (P < 0.01).

CONCLUSIONS

Circulating miR375 can be a reliable biomarker to detect graft damage in clinical islet transplantation because serum C-peptide and proinsulin levels are difficult to interpret due to the influence of multiple factors, such as β-cell stress and physiological response.

摘要

背景

早期且灵敏地检测胰岛移植损伤对于改善移植后结局至关重要。微小RNA 375（miR375）在小动物模型中已被报道为胰腺β细胞死亡的生物标志物。

方法

检测纯化的人胰岛、自体和异体胰岛移植患者以及单纯全胰切除术患者（非移植组）血清中的miR375水平。还在包含人胰岛和自体血液的小型体外试管模型中测定miR375水平。

结果

胰岛中miR375的表达水平呈剂量依赖性（P < 0.001），在体外模型中胰岛损伤后血浆中的miR375水平显著升高（P = 0.003）。临床分析显示，与非移植组相比，自体和异体胰岛移植受者在胰岛输注后7天内循环miR375水平均显著升高（分别为P = 0.005和<0.001）。此外，miR375检测到临床自体移植中3种不同抗炎方案之间胰岛移植损伤的差异（P < 0.01）。