Serum miR-375-3p increase in mice exposed to a high dose of ionizing radiation

Mitsuru Chiba,Sunao Yamada,Chihiro Iwaya,Yoichiro Hosokawa,Satoru Monzen,Andrzej Wojcik,Yuri Kashiwagi,Toshiya Nakamura,Yasushi Mariya

doi:10.1038/s41598-018-19763-7

Mitsuru Chiba, Sunao Yamada + Show 7 more

Open Access

https://doi.org/10.1038/s41598-018-19763-7

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Journal: Scientific Reports	Publication Date: Jan 22, 2018
Citations: 22	License type: open-access

Affiliation: Hirosaki University, Stockholm University

Abstract

Exposure to high-doses of ionizing radiation (IR) leads to development of a strong acute radiation syndrome (ARS) in mammals. ARS manifests after a latency period and it is important to develop fast prognostic biomarkers for its early detection and assessment. Analysis of chromosomal aberrations in peripheral blood lymphocytes is the gold standard of biological dosimetry, but it fails after high doses of IR. Therefore, it is important to establish novel biomarkers of exposure that are fast and reliable also in the high dose range. Here, we investigated the applicability of miRNA levels in mouse serum. We found significantly increased levels of miR-375-3p following whole body exposure to 7 Gy of X-rays. In addition, we analyzed their levels in various organs of control mice and found them to be especially abundant in the pancreas and the intestine. Following a dose of 7 Gy, extensive cell death occurred in these tissues and this correlated negatively with the levels of miR-375-3p in the organs. We conclude that high expressing tissues of miR-375-3p may secrete this miRNA in serum following exposure to 7 Gy. Therefore, elevated miR-375-3p in serum may be a predictor of tissue damage induced by exposure to a high radiation dose.

Highlights

A severe consequence of exposure to high doses of ionizing radiation (IR), whether in consequence of an accident or a deliberate terrorist attach with the use of radiation sources, is the acute radiation syndrome (ARS) involving bone marrow and gastrointestinal necrosis and often leading to multi organ disease syndrome (MODS)
It is known that a whole body dose of 7 Gy X-rays is lethal to mice, involving bone marrow depletion and reduction of peripheral white blood cells (PWBC)[26]
In order to confirm these results and verify that a dose of 7 Gy induces a strong ARS in our mouse model, we monitored the changes of body weight and the level of animal survival over a period of 30 days

Summary

Introduction

A severe consequence of exposure to high doses of ionizing radiation (IR), whether in consequence of an accident or a deliberate terrorist attach with the use of radiation sources, is the acute radiation syndrome (ARS) involving bone marrow and gastrointestinal necrosis and often leading to multi organ disease syndrome (MODS). ARS can be treated by antibiotics, cytokines, blood transfusion and/or stem cell transplantation which prevent infections, excessive immune response and tissue break down, but the treatment success is inversely correlated with the time between radiation exposure and its onset[3,4,5,6,7,8]. MiRNA genes are transcribed by RNA polymerase II into long primary miRNAs (pri-miRNAs) These pri-miRNAs are processed in the nucleus into 70–80 nucleotide precursor miRNAs (pre-miRNAs) by the RNase III enzyme Drosha. Valadi et al discovered that exosomes including various mRNAs and miRNAs were released from cells to extracellular space. These extracellular RNAs can be taken up by other cells[19]. Jacob et al showed that the expression of miR-150, miR-200b, and miR-762 in blood serum of mice changes in relation to the dose of radiation[25]

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