Tenascin-X is increased with decreased expression of miR-378a-5p and miR-486-5p in mice fed a methionine-choline-deficient diet that induces hepatic fibrosis.

IF 1.3 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL
Ken-Ichi Matsumoto, Takuma Higuchi, Mirei Umeki, Masafumi Ono, Shuji Sakamoto
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引用次数: 0

Abstract

We previously reported that tenascin-X (Tnxb) aggravates hepatic fibrosis in mice fed a high-fat and high-cholesterol diet with high levels of phosphorus and calcium (HFCD). In this study, we investigated Tnxb expression in livers with fibrosis caused by administration of a methionine-chorine-deficient (MCD) diet in mice. Whole transcriptome analysis showed that Tnxb was one of the genes with increased expression in livers of MCD diet-fed mice compared with that in livers of normal diet (ND)-fed mice. In microarray and subsequent microRNA (miRNA) network analyses, miR-378a-5p and miR-486-5p were identified in livers of MCD diet-fed mice as downregulated miRNAs, which have their predicted target sites in the 3' untranslated region of Tnxb mRNA and might suppress the translation of Tnxb mRNA. RT-qPCR analyses of livers of MCD diet-fed mice compared with livers of ND-fed mice verified the upregulation of Tnxb and fibrosis-triggering genes and conversely the downregulation of miR-378a-5p and miR-486-5p. Overexpression of miR-378a-5p and miR-486-5p resulted in decreased level not only of the FLAG-tagged fibrinogen-like domain of Tnxb protein (FLAG-mTNX-FG) but also of endogenous Tnxb protein in murine cultured cells. These results indicate that expression of Tnxb is regulated by miR-378a-5p and miR-486-5p in hepatic fibrosis following MCD diet feeding.

蛋氨酸-胆碱缺乏饮食会诱发小鼠肝纤维化,在小鼠体内,随着 miR-378a-5p 和 miR-486-5p 的表达减少,Tenascin-X 也会增加。
我们以前曾报道过,tenascin-X(Tnxb)会加重以高脂肪、高胆固醇和高磷高钙(HFCD)饮食喂养的小鼠的肝纤维化。在这项研究中,我们调查了蛋氨酸-茶碱缺乏(MCD)饮食导致的小鼠肝纤维化中 Tnxb 的表达情况。全转录组分析表明,与正常饮食(ND)喂养的小鼠肝脏相比,Tnxb是MCD饮食喂养的小鼠肝脏中表达增加的基因之一。在微阵列和随后的微RNA(miRNA)网络分析中,MCD饮食喂养小鼠肝脏中的miR-378a-5p和miR-486-5p被确定为下调的miRNA,它们的预测靶位点位于Tnxb mRNA的3'非翻译区,可能会抑制Tnxb mRNA的翻译。对以 MCD 饮食喂养的小鼠肝脏与以 ND 饮食喂养的小鼠肝脏进行的 RT-qPCR 分析验证了 Tnxb 和纤维化触发基因的上调,以及相反的 miR-378a-5p 和 miR-486-5p 的下调。miR-378a-5p和miR-486-5p的过表达不仅导致FLAG标记的Tnxb蛋白纤溶酶原样结构域(FLAG-mTNX-FG)水平下降,还导致小鼠培养细胞中内源性Tnxb蛋白水平下降。这些结果表明,MCD饮食喂养后肝纤维化过程中,Tnxb的表达受miR-378a-5p和miR-486-5p的调控。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biomedical Research-tokyo
Biomedical Research-tokyo 医学-医学:研究与实验
CiteScore
2.40
自引率
0.00%
发文量
19
审稿时长
>12 weeks
期刊介绍: Biomedical Research is peer-reviewed International Research Journal . It was first launched in 1990 as a biannual English Journal and later became triannual. From 2008 it is published in Jan-Apr/ May-Aug/ Sep-Dec..
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