检索结果-南通市图书馆

Gene expression profiles of hepatic cell-type specific marker genes in progression of liver fibrosis

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2006年第40期12卷 6473-6499页

作者： Yoshiyuki Takahara Mitsuo Takahashi Hiroki Wagatsuma Fumihiko Yokoya Qing-Wei Zhang Mutsuyo Yamaguchi hiroyuki aburatani Norifumi Kawada Exploratory and Applied Pharmaceutical Research Department Pharmaceutical Company Ajinomoto Co. Inc Kawasaki 210-8681 Japan Biochemical Information project BiolT Business Development Group Fujitsu Limited Tokyo Japan Center for Collaborative Research Research Center for Advanced Science and Technology the University of Tokyo Tokyo Japan Department of Hepatology Graduate School of Medicine Osaka City University Osaka Japan

AIM: To determine the gene expression profile data for the whole liver during development of dimethylni-trosamine (DMN)-induced hepatic ***: Marker genes were identified for different types of hepatic cells, including hepatic stellate cells (HSCs), Kupffer cells (including other inflammatory cells), and hepatocytes, using independent temporal DNA microarray data obtained from isolated hepatic cells. RESULTS: The cell-type analysis of gene expression gave several key results and led to formation of three hypotheses: (1) changes in the expression of HSC-specific marker genes during fibrosis were similar to gene expression data in in vitro cultured HSCs, suggesting a major role of the self-activating characteristics of HSCs in formation of fibrosis; (2) expression of mast cell-specific marker genes reached a peak during liver fibrosis, suggesting a possible role of mast cells in formation of fibrosis; and (3) abnormal expression of hepatocyte-specific marker genes was found across several metabolic pathways during fibrosis, including sulfur-containing amino acid metabolism, fatty acid metabolism, and drug metabolism, suggesting a mechanistic relationship between these abnormalities and symptoms of liver fibrosis. CONCLUSION: Analysis of marker genes for specific hepatic cell types can identify the key aspects of fibro-genesis. Sequential activation of inflammatory cells and the self-supporting properties of HSCs play an important role in development of fibrosis.

关键词： Liver fibrosis Gene expression Microarray Dimethylnitrosamine Marker genes Hepatic stellate cell Kupffer cell Hepatocytes Metabolic pathway

Epigenetic alteration to activate Bmp2-Smad signaling in Raf-induced senescence

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Biological Chemistry 2016年第1期7卷 188-205页

作者： Mai Fujimoto Yasunobu Mano Motonobu Anai Shogo Yamamoto Masaki Fukuyo hiroyuki aburatani Atsushi Kaneda Genome Science Division Research Center for Advanced Science and Technologythe University of Tokyo Department of Molecular Oncology Graduate School of MedicineChiba University Laboratory for Systems Biology and Medicine Research Center for Advanced Science and Technologythe University of Tokyo CREST Japan Agency for Medical Research and Development

AIM: To investigate epigenomic and gene expression alterations during cellular senescence induced by oncogenic Raf. METHODS: Cellular senescence was induced into mouse embryonic fibroblasts(MEFs) by infecting retrovirus to express oncogenic Raf(RafV 600E). RNA was collected from RafV 600 E cells as well as MEFs without infection and MEFs with mock infection, and a genome-wide gene expression analysis was performed using microarray. The epigenomic status for active H3K4me3 and repressive H3K27me3 histone marks was analyzed by chromatin immunoprecipitation-sequencing for RafV 600 E cells on day 7 and for MEFs without infection. These data for Raf-induced senescence were compared with data for Ras-induced senescence that were obtained in our previous study. Gene knockdown and overexpression were done by retrovirus infection. RESULTS: Although the expression of some genes including secreted factors was specifically altered in either Ras- or Raf-induced senescence, many genes showed similar alteration pattern in Raf- and Ras-induced senescence. A total of 841 commonly upregulated 841 genes and 573 commonly downregulated genes showed a significant enrichment of genes related to signal and secreted proteins, suggesting the importance of alterations in secreted factors. Bmp2, a secreted protein to activate Bmp2-Smad signaling, was highly upregulated with gain of H3K4me3 and loss of H3K27me3 during Raf-induced senescence, as previously detected in Ras-induced senescence, and the knockdown of Bmp2 by sh RNA lead to escape from Raf-induced senescence. Bmp2-Smad inhibitor Smad6 was strongly repressed with H3K4me3 loss in Raf-induced senescence, as detected in Ras-induced senescence, and senescence was also bypassed by Smad6 induction in Raf-activated cells. Different from Ras-induced senescence, however, gain of H3K27me3 did not occur in the Smad6 promoter region during Raf-induced senescence. When comparing genome-wide alteration between Ras- and Raf-induced senescence, genes

关键词： Senescence Epigenome Raf H3K27me3 Histone Ras

Development of an Algorithm for Reconstructing a Comprehensive Pathway Model: Application to <i>Saccharomyces cerevisiae</i>

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Biomedical Science and Engineering 2015年第8期8卷 500-510页

作者： Itaru Takeda Masayuki Machida Sachiyo aburatani Department of Biotechnology and Life Science Tokyo University of Agriculture and Technology Naka-cho Koganei Tokyo Japan Biotechnology Research Institute for Drug Discovery National Institute of Advanced Industrial Science and Technology (AIST) Tokyo Waterfront Bio-IT Research Building Aomi Koto-ku Tokyo Japan Bioproduction Research Institute National Institute of Advanced Industrial Science and Technology (AIST) Higashi-nijo Tsukisamu Sapporo Japan

The generation of bioactive products by microbial bioprocesses is important for drug discovery, functional food development, and other beneficial purposes. Many pathways contribute to the production of these bioactive compounds, but important knowledge for improving productivity still remains in hidden pathways. Recently, an abundance of knowledge about metabolic pathways has been accumulated in metabolic pathway databases, such as BioCyc and KEGG. Many by-products are chemically transformed and actually used in other enzymatic reactions. In this work, we developed an algorithm for the reconstruction of a comprehensive genetic pathway model from a known metabolic pathway database. This model considers the interactions of the by-products, in addition to the main products. Furthermore, we developed a method for the construction of a comprehensive pathway model in a specific organism. In this study, we reconstructed a Saccharomyces cerevisiae model. From this model, the pathways among enzymes that contributed to galactose metabolism were explored. Using S. cerevisiae DNA microarray data, the activated pathways were found among the explored pathways.

关键词： Bioinformatics Metabolic Pathway

Exploration of Activated Pathways for Improving Antifungal Agent FR901469 Productivity in Fungal Species No.11243 Using Comprehensive Pathway Model

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Biosciences and Medicines 2017年第7期5卷 16-31页

作者： Itaru Takeda Hiroya Itoh Makoto Matsui Takashi Shibata Masayuki Machida Sachiyo aburatani Department of Biotechnology and Life Science Tokyo University of Agriculture and Technology Tokyo Japan Biotechnology Research Institute for Drug Discovery National Institute of Advanced Industrial Science and Technology (AIST) Tokyo Japan Astellas Pharma Inc. Tsukuba Biotechnology Research Center Ibaraki Japan Bioproduction Research Institute National Institute of Advanced Industrial Science and Technology (AIST) Sapporo Japan Computational Bio Big-Data Open Innovation Laboratory (CBBD-OIL) Tokyo Japan

Secondary metabolites are important for various industrial applications. The production of secondary metabolites is often improved by the activation of substrate supply pathways for biosynthesis. However, many important pathways have remained unclear. In this study, we explored possible pathways related to substrate supply for the biosynthesis of the antifungal agent FR901469 which is a nonribosomal peptide and a fungal secondary metabolite. To clarify the unknown activated pathways, we utilized the Comprehensive Pathway Model (CPM) which was developed in our previous study. We verified that the overexpression of the hypothetical beta-alanine-aminotransferase (BAL-AT), which was included in the explored pathways, improved the FR901469 productivity. The genes encoding the BAL metabolic enzymes are considered to be important for improving the FR901469 productivity.

关键词： Bioinformatics Metabolic Pathway Model Fungi Secondary Metabolites