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循环 microRNA-375 作为胰岛β细胞死亡的生物标志物和细胞保护化合物对胰岛β细胞质量的保护作用。

Circulating microRNA-375 as biomarker of pancreatic beta cell death and protection of beta cell mass by cytoprotective compounds.

机构信息

Cell Differentiation Lab, Vrije Universiteit Brussel (VUB), Brussels, Belgium.

Diabetes Research Center, Vrije Universiteit Brussel (VUB), Brussels, Belgium.

出版信息

PLoS One. 2017 Oct 17;12(10):e0186480. doi: 10.1371/journal.pone.0186480. eCollection 2017.

DOI:10.1371/journal.pone.0186480
PMID:29040320
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5645134/
Abstract

OBJECTIVE

Previous studies demonstrated that circulating microRNA-375 (miR-375) is a suitable plasma biomarker for real-time detection of beta cell death. The present study evaluated the use of this biomarker to assess the beta cytoprotective effect of phenylpropenoic acid glucoside (PPAG), which was previously demonstrated to protect beta cells against various types of injury, and of exendin-4, which is an established antidiabetic drug.

METHODS

PPAG or exendin-4 were administered in mice treated with streptozotocin (STZ) to acutely induce beta cell death. Beta cell mass and apoptotic death were measured in pancreatic tissue sections. Circulating miR-375 was measured in blood plasma by RT-qPCR. The release of miR-375 was also measured in vitro by MIN-6 beta cells.

RESULTS

Administration of STZ resulted in measurable circulating levels of miR-375, a decrease in beta cell mass and increase in frequency of apoptotic beta cells. In vitro, there was a good correlation between miR-375 release and the extent of beta cell death. Treatment of mice with PPAG or exendin-4 significantly attenuated STZ-induced loss of beta cell mass and beta cell apoptosis, and normalized the blood level of miR-375.

CONCLUSIONS

These findings show the potential use of serological miR-375 measurements to evaluate the beta cytoprotective effect of (potential) antidiabetic drugs in vivo.

摘要

目的

先前的研究表明，循环 microRNA-375（miR-375）是实时检测β细胞死亡的合适血浆生物标志物。本研究评估了该生物标志物用于评估苯丙烯酸葡萄糖苷（PPAG）的β细胞保护作用，先前的研究表明 PPAG 可保护β细胞免受各种类型的损伤，以及 exendin-4 的作用，后者是一种已确立的抗糖尿病药物。

方法

在链脲佐菌素（STZ）处理的小鼠中给予 PPAG 或 exendin-4，以急性诱导β细胞死亡。在胰腺组织切片中测量β细胞质量和凋亡死亡。通过 RT-qPCR 在血浆中测量循环 miR-375。还通过 MIN-6 β细胞测量 miR-375 的体外释放。

结果

STZ 的给药导致可测量的循环 miR-375 水平、β细胞质量下降和凋亡β细胞频率增加。在体外，miR-375 的释放与β细胞死亡的程度之间存在良好的相关性。用 PPAG 或 exendin-4 治疗小鼠可显著减轻 STZ 诱导的β细胞质量损失和β细胞凋亡，并使血液 miR-375 水平正常化。

结论

这些发现表明血清 miR-375 测量可能用于评估体内（潜在）抗糖尿病药物的β细胞保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f8/5645134/e4ea8f7d58b7/pone.0186480.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f8/5645134/276effb8c537/pone.0186480.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f8/5645134/ec6b75494154/pone.0186480.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f8/5645134/abe37231e357/pone.0186480.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f8/5645134/a902f0331bdf/pone.0186480.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f8/5645134/e4ea8f7d58b7/pone.0186480.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f8/5645134/276effb8c537/pone.0186480.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f8/5645134/ec6b75494154/pone.0186480.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f8/5645134/abe37231e357/pone.0186480.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f8/5645134/a902f0331bdf/pone.0186480.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f8/5645134/e4ea8f7d58b7/pone.0186480.g005.jpg

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