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C57BL/6小鼠造血祖细胞中苯诱导的异常miRNA表达谱

Benzene-Induced Aberrant miRNA Expression Profile in Hematopoietic Progenitor Cells in C57BL/6 Mice.

作者信息

Wei Haiyan, Zhang Juan, Tan Kehong, Sun Rongli, Yin Lihong, Pu Yuepu

机构信息

Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.

出版信息

Int J Mol Sci. 2015 Nov 12;16(11):27058-71. doi: 10.3390/ijms161126001.

Abstract

Benzene is a common environmental pollutant that causes hematological alterations. MicroRNAs (miRNAs) may play a role in benzene-induced hematotoxicity. In this study, C57BL/6 mice showed significant hematotoxicity after exposure to 150 mg/kg benzene for 4 weeks. Benzene exposure decreased not only the number of cells in peripheral blood but also hematopoietic progenitor cells in the bone marrow. Meanwhile, RNA from Lin(-) cells sorted from the bone marrow was applied to aberrant miRNA expression profile using Illumina sequencing. We found that 5 miRNAs were overexpressed and 45 miRNAs were downregulated in the benzene exposure group. Sequencing results were confirmed through qRT-PCR. Furthermore, we also identified five miRNAs which significantly altered in Lin(-)c-Kit⁺ cells obtained from benzene-exposed mice, including mmu-miR-34a-5p; mmu-miR-342-3p; mmu-miR-100-5p; mmu-miR-181a-5p; and mmu-miR-196b-5p. In summary, we successfully established a classical animal model to induce significant hematotoxicity by benzene injection. Benzene exposure may cause severe hematotoxicity not only to blood cells in peripheral circulation but also to hematopoietic cells in bone marrow. Benzene exposure also alters miRNA expression in hematopoietic progenitor cells. This study suggests that benzene induces alteration in hematopoiesis and hematopoiesis-associated miRNAs.

摘要

苯是一种常见的环境污染物,可导致血液学改变。微小RNA(miRNA)可能在苯诱导的血液毒性中发挥作用。在本研究中,C57BL/6小鼠在暴露于150mg/kg苯4周后表现出显著的血液毒性。苯暴露不仅减少了外周血中的细胞数量,还减少了骨髓中的造血祖细胞数量。同时,将从骨髓中分选的Lin(-)细胞的RNA用于Illumina测序以检测异常的miRNA表达谱。我们发现苯暴露组中有5种miRNA过表达,45种miRNA下调。测序结果通过qRT-PCR得到证实。此外,我们还鉴定了从苯暴露小鼠获得的Lin(-)c-Kit⁺细胞中显著改变的5种miRNA,包括mmu-miR-34a-5p、mmu-miR-342-3p、mmu-miR-10y-5p、mmu-miR-181a-5p和mmu-miR-196b-5p。总之,我们成功建立了一个通过注射苯诱导显著血液毒性的经典动物模型。苯暴露不仅可能对外周循环中的血细胞造成严重血液毒性,还可能对骨髓中的造血细胞造成严重血液毒性。苯暴露还会改变造血祖细胞中的miRNA表达。本研究表明苯会诱导造血及造血相关miRNA的改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0952/4661859/d9780c010af1/ijms-16-26001-g001.jpg

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