Aberrant expression of miR-451a contributes to 1,2-dichloroethane-induced hepatic glycerol gluconeogenesis disorder by inhibiting glycerol kinase expression in NIH Swiss mice.
Aberrant expression of miR-451a contributes to 1,2-dichloroethane-induced hepatic glycerol gluconeogenesis disorder by inhibiting glycerol kinase expression in NIH Swiss mice.
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miR-451a 的异常表达通过抑制 NIH Swiss 小鼠中的甘油激酶表达，导致 1,2-二氯乙烷诱导的肝甘油糖异生障碍。
DOI：
10.1002/jat.3526
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发表时间：
2017
影响因子：
3.3
通讯作者：
Wang Qing
中科院分区：
文献类型：
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作者：
Zeng Ni;Jiang Hongmei;Fan Qiming;Wang Ting;Rong Weifeng;Li Guoliang;Li Ruobi;Xu D;an;Guo Tao;Wang Fei;Zeng Lihai;Huang Manqi;Zheng Jiewei;Lu Fengrong;Chen Wen;Hu Qiansheng;Huang Zhenlie;Wang Qing
对化学性肝功能不全过程中微小RNA(MiRNA)异常表达的鉴定将有助于更好地理解miRNA在肝病中的重要作用。1，2-二氯乙烷(1，2-DCE)是一种氯化有机毒物，可导致职业接触人群的肝脏异常。为了探讨miRNA的异常表达是否与1，2-DCE暴露所介导的肝脏异常有关，我们研究了动态吸入350或700 mg m-31，2-DCE 28天后，NIH瑞士小鼠肝脏miRNA表达模式的变化。使用微阵列芯片，我们发现只有mmumiR-451a在暴露于700 mg m-31，2-DCE的小鼠肝组织中显著上调；这一发现通过实时定量聚合酶链式反应得到了验证。体外研究表明，导致小鼠AML12细胞MMU-miR-451a表达上调的是代谢产物2-氯乙酸，而不是1，2-DCE。此外，2-氯乙酸诱导MMU-miR-451a的表达上调可抑制小鼠肝组织和AML12细胞中甘油激酶的表达，导致甘油糖异生的抑制。这些观察结果为肝脏MMU-miR-451a对1，2-DCE暴露的反应提供了证据，并可能通过抑制甘油的糖异生过程而导致葡萄糖代谢紊乱。
The identification of aberrant microRNA (miRNA) expression during chemical‐induced hepatic dysfunction will lead to a better understanding of the substantial role of miRNAs in liver diseases. 1,2‐Dichloroethane (1,2‐DCE), a chlorinated organic toxicant, can lead to hepatic abnormalities in occupationally exposed populations. To explore whether aberrant miRNA expression is involved in liver abnormalities mediated by 1,2‐DCE exposure, we examined alterations in miRNA expression patterns in the livers of NIH Swiss mice after dynamic inhalation exposure to 350 or 700 mg m–31,2‐DCE for 28 days. Using a microarray chip, we discovered that only mmumiR‐451a was significantly upregulated in the liver tissue of mice exposed to 700 mg m–31,2‐DCE; this finding was validated by quantitative real‐time polymerase chain reaction. In vitro study revealed that it was metabolite 2‐chloroacetic acid, not 1,2‐DCE that resulted in the upregulation of mmu‐miR‐451a in the mouse AML12 cell line. Furthermore, our data showed that the upregulation of mmu‐miR‐451a induced by 2‐chloroacetic acid could suppress the expression of glycerol kinase and lead to the inhibition of glycerol gluconeogenesis in mouse liver tissue and AML12 cells. These observations provide evidence that hepatic mmu‐miR‐451a responds to 1,2‐DCE exposure and might induce glucose metabolism disorders by suppressing the glycerol gluconeogenesis process.