Sho-saiko-to, a traditional herbal medicine, regulates gene expression and biological function by way of microRNAs in primary mouse hepatocytes

BMC Complementary and Alternative Medicine

Research Article

Bu-Yeo Kim¹  Yun Hee Kim¹  Kwang Hoon Song² 

[1] Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, 305-811, Yuseong-gu, Daejeon, Republic of Korea;SME Partnership Center, Korea Institute of Oriental Medicine, 305-811, Daejeon, Republic of Korea;University of Science and Technology, 217 Gajeong-ro, 305-333, Yuseong-gu, Daejeon, Republic of Korea;

关键词: Sho-saiko-to;    Microarray;    MicroRNA;    Hepatocyte;    Pathway;    Promoter;   

DOI  :  10.1186/1472-6882-14-14

 received in 2013-09-16, accepted in 2013-12-31,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundSho-saiko-to (SST) (also known as so-shi-ho-tang or xiao-chai-hu-tang) has been widely prescribed for chronic liver diseases in traditional Oriental medicine. Despite the substantial amount of clinical evidence for SST, its molecular mechanism has not been clearly identified at a genome-wide level.MethodsBy using a microarray, we analyzed the temporal changes of messenger RNA (mRNA) and microRNA expression in primary mouse hepatocytes after SST treatment. The pattern of genes regulated by SST was identified by using time-series microarray analysis. The biological function of genes was measured by pathway analysis. For the identification of the exact targets of the microRNAs, a permutation-based correlation method was implemented in which the temporal expression of mRNAs and microRNAs were integrated. The similarity of the promoter structure between temporally regulated genes was measured by analyzing the transcription factor binding sites in the promoter region.ResultsThe SST-regulated gene expression had two major patterns: (1) a temporally up-regulated pattern (463 genes) and (2) a temporally down-regulated pattern (177 genes). The integration of the genes and microRNA demonstrated that 155 genes could be the targets of microRNAs from the temporally up-regulated pattern and 19 genes could be the targets of microRNAs from the temporally down-regulated pattern. The temporally up-regulated pattern by SST was associated with signaling pathways such as the cell cycle pathway, whereas the temporally down-regulated pattern included drug metabolism-related pathways and immune-related pathways. All these pathways could be possibly associated with liver regenerative activity of SST. Genes targeted by microRNA were moreover associated with different biological pathways from the genes not targeted by microRNA. An analysis of promoter similarity indicated that co-expressed genes after SST treatment were clustered into subgroups, depending on the temporal expression patterns.ConclusionsWe are the first to identify that SST regulates temporal gene expression by way of microRNA. MicroRNA targets and non-microRNA targets moreover have different biological roles. This functional segregation by microRNA would be critical for the elucidation of the molecular activities of SST.

【 授权许可】

Unknown   
© Song et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.