8 results on '"Mizuho Nakayama"'
Search Results
2. RNaseH2A Downregulation Drives Chromosomal DNA Fragmentation and Accumulation of RNA-DNA Hybrids in Senescent Cells
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Kenichi Miyata, Akiko Takahashi, Tze Mun Loo, Mizuho Nakayama, Shizuo Kaji, Eiji Hara, Ryo Okada, Yoshiro Maezawa, Akira Nakanishi, Kaoru Katoh, Keiyo Takubo, Satoshi Nagayama, Koji Nagao, Glen N. Barber, Masato T. Kanemaki, Sho Sugawara, Chikashi Obuse, Koutaro Yokote, and Masanobu Oshima more...
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genomic DNA ,Downregulation and upregulation ,Nucleolus ,Gene expression ,medicine ,Fragmentation (cell biology) ,Biology ,medicine.disease ,E2F ,Transcription factor ,Werner syndrome ,Cell biology - Abstract
Cellular senescence caused by oncogenic stimuli is related to the development of various age-related diseases via senescence-associated secretory phenotype (SASP). Recent studies have revealed that the SASP is induced via the cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway. However, the molecular mechanism of nucleotide ligand production for these cytoplasmic sensors remains unclear. Here, we discover that the expression of RNaseH2A is regulated by E2F transcription factor and decreases during cellular senescence, thus abnormally incorporated ribonucleoside monophosphates (rNMPs) cause genomic DNA fragmentation, while excess R-loop structures lead to RNA-DNA hybrid accumulation in the nucleoli and cytoplasm of senescent cells. Consequently, both chromosomal DNA fragments and RNA-DNA hybrids induce aberrant activation of the cGAS-STING pathway and SASP-factor gene expression. Furthermore, RNaseH2A reduction was associated with pathological features and poor prognoses in individuals with Werner syndrome and cervical, ovarian and colorectal cancers. Our findings provide new insights into how nucleotide ligand production relates to SASP induction. more...
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- 2020
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3. Interleukin 1 Up-regulates MicroRNA 135b to Promote Inflammation-Associated Gastric Carcinogenesis in Mice
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Liang Yu, Seong-Jin Kim, Han-Kwang Yang, Kazuhiro Murakami, Dominic Chih-Cheng Voon, Chan Young Ock, Kanae Echizen, Toshinari Minamoto, Mizuho Nakayama, Masanobu Oshima, Hiroko Oshima, Zachary Wei Ern Yong, Brendan J. Jenkins, Tae Su Han, and Eri Sakai more...
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0301 basic medicine ,Carcinogenesis ,Stomach Cancer ,Cell Cycle Proteins ,Biology ,GPI-Linked Proteins ,medicine.disease_cause ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Stomach Neoplasms ,Cell Line, Tumor ,microRNA ,Gastric mucosa ,medicine ,Animals ,Humans ,RNA, Messenger ,Stomach cancer ,Oncogene ,Gene knockdown ,Hyperplasia ,Hepatology ,Gastroenterology ,Wnt signaling pathway ,Interleukin ,Forkhead Transcription Factors ,medicine.disease ,Up-Regulation ,Organoids ,Repressor Proteins ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Gastric Mucosa ,Gastritis ,Gene Knockdown Techniques ,Cancer cell ,Tumor Progression ,Cancer research ,030211 gastroenterology & hepatology ,Interleukin-1 ,Signal Transduction - Abstract
金沢大学ナノ生命科学研究所, Background & Aims: Gastritis is associated with development of stomach cancer, but little is known about changes in microRNA expression patterns during gastric inflammation. Specific changes in gene expression in epithelial cells are difficult to monitor because of the heterogeneity of the tissue. We investigated epithelial cell-specific changes in microRNA expression during gastric inflammation and gastritis-associated carcinogenesis in mice. Methods: We used laser microdissection to enrich epithelial cells from K19-C2mE transgenic mice, which spontaneously develop gastritis-associated hyperplasia, and Gan mice, which express activated prostaglandin E2 and Wnt in the gastric mucosa and develop gastric tumors. We measured expression of epithelial cell-enriched microRNAs and used bioinformatics analyses to integrate data from different systems to identify inflammation-associated microRNAs. We validated our findings in gastric tissues from mice and evaluated protein functions in gastric cell lines (SNU-719, SNU-601, SNU-638, AGS, and GIF-14) and knockout mice. Organoids were cultured from gastric corpus tissues of wild-type and miR-135b–knockout C57BL/6 mice. We measured levels of microRNAs in pairs of gastric tumors and nontumor mucosa from 28 patients in Japan. Results: We found microRNA 135b (miR-135B) to be the most overexpressed microRNA in gastric tissues from K19-C2mE and Gan mice: levels increased during the early stages of gastritis-associated carcinogenesis. Levels of miR-135B were also increased in gastric tumor tissues from gp130 F/F mice and patients compared with nontumor tissues. In gastric organoids and immortalized cell lines, expression of miR-135B was induced by interleukin 1 signaling. K19-C2mE mice with disruption of Mir-135b developed hyperplastic lesions that were 50% smaller than mice without Mir-135b disruption and had significant reductions in cell proliferation. Expression of miR-135B in gastric cancer cell lines increased their colony formation, migration, and sphere formation. We identified FOXN3 and RECK messenger RNAs (mRNAs) as targets of miR-135B; their knockdown reduced migration of gastric cancer cell lines. Levels of FOXN3 and RECK mRNAs correlated inversely with levels of miR-135B in human gastric tumors and in inflamed mucosa from K19-C2mE mice. Conclusions: We found expression of miR-135B to be up-regulated by interleukin L1 signaling in gastric cancer cells and organoids. miR-135B promotes invasiveness and stem-cell features of gastric cancer cells in culture by reducing FOXN3 and RECK messenger RNAs. Levels of these messenger RNA targets, which encode tumor suppressor, are reduced in human gastric tumors. © 2019 AGA Institute, Embargo Period 12 months more...
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- 2019
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4. The Lipid Mediator Protectin D1 Inhibits Influenza Virus Replication and Improves Severe Influenza
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Tokiko Watanebe, Takaaki Nakaya, Makoto Murakami, Hiroki Nakanishi, Keiji Kuba, Josef M. Penninger, Yoshihiro Kawaoka, Jun Katahira, Takayo Ohto, Masayuki Morita, Ayumi Kadowaki, Akihiko Ichikawa, Saori Sakabe, Shota Nakamura, Hiroyuki Arai, Ryo Iwamoto, Ryo Taguchi, Mizuho Nakayama, Yumiko Imai, Makoto Arita, Tomo Daidoji, and Yoshihiro Yoneda more...
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Docosahexaenoic Acids ,Active Transport, Cell Nucleus ,Biology ,Protectin D1 ,Virus Replication ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Virus ,Cell Line ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Influenza A Virus, H1N1 Subtype ,0302 clinical medicine ,Mediator ,Orthomyxoviridae Infections ,Pandemic ,Influenza A virus ,medicine ,Animals ,Humans ,030304 developmental biology ,0303 health sciences ,Influenza A Virus, H5N1 Subtype ,Biochemistry, Genetics and Molecular Biology(all) ,virus diseases ,Lipid signaling ,Virology ,Influenza A virus subtype H5N1 ,3. Good health ,Viral replication ,chemistry ,030220 oncology & carcinogenesis - Abstract
SummaryInfluenza A viruses are a major cause of mortality. Given the potential for future lethal pandemics, effective drugs are needed for the treatment of severe influenza such as that caused by H5N1 viruses. Using mediator lipidomics and bioactive lipid screen, we report that the omega-3 polyunsaturated fatty acid (PUFA)-derived lipid mediator protectin D1 (PD1) markedly attenuated influenza virus replication via RNA export machinery. Production of PD1 was suppressed during severe influenza and PD1 levels inversely correlated with the pathogenicity of H5N1 viruses. Suppression of PD1 was genetically mapped to 12/15-lipoxygenase activity. Importantly, PD1 treatment improved the survival and pathology of severe influenza in mice, even under conditions where known antiviral drugs fail to protect from death. These results identify the endogenous lipid mediator PD1 as an innate suppressor of influenza virus replication that protects against lethal influenza virus infection. more...
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- 2013
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5. Beneficial effect of a synthetic prostacyclin agonist, ONO-1301, in rat autoimmune myocarditis model
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Daiju Fukuda, Hirotsugu Yamada, Shusuke Yagi, Tetsuya Kitagawa, Kunio Matsumoto, Mizuho Nakayama, Michio Shimabukuro, Yoichiro Hirata, Etsuko Uematsu, Yoshiki Sakai, Masataka Sata, Takeshi Soeki, and Hirotsugu Kurobe more...
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Cardiomyopathy, Dilated ,Male ,Agonist ,medicine.medical_specialty ,Myocarditis ,Pyridines ,medicine.drug_class ,Cardiomyopathy ,Administration, Oral ,Prostacyclin ,Myosins ,Autoimmune Diseases ,Internal medicine ,Natriuretic Peptide, Brain ,medicine ,Animals ,Pharmacology ,business.industry ,Stem Cells ,Hemodynamics ,Endothelial Cells ,Dilated cardiomyopathy ,medicine.disease ,Brain natriuretic peptide ,Rats ,Disease Models, Animal ,Endocrinology ,Rats, Inbred Lew ,Heart failure ,Hepatocyte growth factor ,business ,medicine.drug - Abstract
Injury to the heart can result in cardiomyocyte hypertrophy, fibrosis, and cell death. Myocarditis sometimes progresses to dilated cardiomyopathy. We previously reported that ONO-1301, a synthetic prostacyclin agonist with thromboxane-synthase inhibitory activity, promotes production of hepatocyte growth factor (HGF) from various cell types and ameliorates ischemia-induced left ventricle dysfunction in the mouse, rat and pig. Here, we investigated the therapeutic efficacy of ONO-1301 in a rat model of myosin-induced experimental autoimmune myocarditis, in which the heart transits from an acute inflammatory phase to a chronic dilated cardiomyopathy phase. Four weeks after myosin injection to Lewis rats, ONO-1301 (6 mg/kg/day) was orally administered for 4 weeks (ONO-1301 group). Hemodynamic parameters and plasma brain natriuretic peptide (BNP) level were significantly improved by ONO-1301. Histological analysis revealed that capillary density in the myocardium was significantly increased by ONO-1301. ONO-1301 increased circulating endothelial progenitor cells (EPC) as determined by FACS analysis. These beneficial effects of ONO-1301 were partially abrogated by a neutralizing anti-HGF antibody (8 mg/kg/dose). These findings indicate beneficial effects of ONO-1301 in a rat experimental autoimmune myocarditis model. more...
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- 2013
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6. A synthetic prostacyclin agonist, ONO-1301, ameliorates ventricular remodeling after acute myocardial infarction via upregulation of HGF in rat
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Hirotsugu Yamada, Mizuho Nakayama, Kunio Matsumoto, Yoshiki Sakai, Masataka Sata, Yoichiro Hirata, Michio Shimabukuro, Asuka Shiota, Takeshi Soeki, and Takashi Igarashi
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Agonist ,Aging ,medicine.medical_specialty ,business.industry ,medicine.drug_class ,Prostacyclin ,Pharmacology ,medicine.disease ,Pathology and Forensic Medicine ,Coronary arteries ,Vascular endothelial growth factor ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Internal medicine ,medicine ,Cardiology ,Hepatocyte growth factor ,Myocardial infarction ,Geriatrics and Gerontology ,Ligation ,business ,Ventricular remodeling ,medicine.drug - Abstract
It has been shown that administration of angiogenic factors can augment collateral growth in ischemic tissues. We previously reported that ONO-1301, a synthetic prostacyclin agonist with thromboxane-synthase inhibitory activity, promotes production of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) from various cell types. We evaluated therapeutic efficacy of ONO-1301 in rat cardiac ischemia model. Ligation of left anterior descending coronary arteries was performed to 10-week-old Wistar rats, and the slow releasing form of ONO-1301 was administrated subcutaneously 3 days after the ligation (control group and ONO-1301 group). Hemodynamic parameters and plasma BNP levels were significantly improved by ONO-1301. Histological analysis revealed that ONO-1301 suppressed fibrotic changes in the myocardium (27.7±3.1% vs 23.3±3.6%, p more...
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- 2011
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7. Wnt9a secreted from the walls of hepatic sinusoids is essential for morphogenesis, proliferation, and glycogen accumulation of chick hepatic epithelium
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Rika Miki, Ken Matsumoto, Norifumi Tatsumi, Mizuho Nakayama, and Yuji Yokouchi
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Sinusoid ,medicine.medical_specialty ,Frizzled ,Liver cytology ,Hepatic epithelium ,Proliferation ,Septum transversum ,Morphogenesis ,Biology ,Polymerase Chain Reaction ,Wnt ,RNA interference ,Internal medicine ,In Situ Nick-End Labeling ,medicine ,Animals ,Hepatocyte ,Molecular Biology ,DNA Primers ,Epithelial–vascular interaction ,Hepatic Cord ,Stem cell ,Liver development ,Wnt signaling pathway ,Epithelial Cells ,Cell Biology ,β-catenin ,Hepatic cord ,Immunohistochemistry ,Frizzled Receptors ,Cell biology ,Wnt Proteins ,Endocrinology ,medicine.anatomical_structure ,Liver ,Short hairpin ,Differentiation ,Hepatic stellate cell ,Hepatogenesis ,Hepatocellular cord ,Chickens ,Cell Division ,Hepatoblast ,Developmental Biology - Abstract
Hepatic epithelial morphogenesis, including hepatoblast migration and proliferation in the septum transversum, requires the interaction of hepatic epithelium with the embryonic sinusoidal wall. No factors that mediate this interaction have yet been identified. As the beta-catenin pathway is active in hepatoblast proliferation, then Wnt ligands might activate the canonical Wnt pathway during liver development. Here, we investigated the role of Wnts in mediating epithelial vessel interactions in the developing chick liver. We found that Wnt9a was specifically expressed in both endothelial and stellate cells of the embryonic sinusoidal wall. Induced overexpression of Wnt9a resulted in hepatomegaly with hyperplasia of the hepatocellular cords, and in hyperproliferation of hepatocytes. Knockdown of Wnt9a caused a reduction in liver size, with hypoplasia of hepatocellular cord branching, and hypoproliferation of hepatoblasts, and also inhibited glycogen accumulation at later developmental stages. Wnt9a promoted in vivo stabilization of beta-catenin through binding with Frizzled 4, 7, and 9, and activated TOPflash reporter expression in vitro via Frizzled 7 and 9. Our results demonstrate that Wnt9a from the embryonic sinusoidal wall is required for the proper morphogenesis of chick hepatocellular cords, proliferation of hepatoblasts/hepatocytes, and glycogen accumulation in hepatocytes. Wnt9a signaling appears to be mediated by an Fzd7/9-beta-catenin pathway. more...
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- 2008
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8. Id3 is important for proliferation and differentiation of the hepatoblasts during the chick liver development
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Yuji Yokouchi, Masaaki Yanai, Norifumi Tatsumi, Mizuho Nakayama, and Ken Matsumoto
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medicine.medical_specialty ,Programmed cell death ,Embryology ,Cell growth ,Liver cytology ,Cellular differentiation ,Regulator ,Cell Differentiation ,Chick Embryo ,Biology ,Embryonic stem cell ,Cell biology ,Avian Proteins ,Endocrinology ,medicine.anatomical_structure ,Liver ,Internal medicine ,Hepatocytes ,medicine ,Animals ,Inhibitor of Differentiation Proteins ,Endoderm ,Cell Proliferation ,Progenitor ,Developmental Biology - Abstract
The specified hepatic endoderm (hepatoblasts), the bipotential progenitor for hepatocytes and bile duct epithelial cells, proliferates during the primordial stages of liver development. Despite extensive studies, the mechanism that regulates proliferation of bipotential hepatoblasts is not fully understood. Here we show that Id3, a negative regulator of helix-loop-helix transcription factors, is an important regulator of hepatoblast proliferation in the developing chick liver. Id3 was expressed in hepatoblasts at early developmental stages (stages 12-29) but not in hepatocytes at later developmental stages (stage 34 onwards). Depletion of Id3 in hepatoblasts by siRNA results in failure of cell proliferation, but is not associated with either cell death or failure of expression of Hhex and Fibrinogen, the earliest hepatoblast markers. These observations suggest that at early developmental stages, Id3 functions as a positive regulator of hepatoblast proliferation, independent of cell death or maintenance of the non-terminally differentiated state. Interestingly at later developmental stages, the expression pattern of Id3 is complementary to that of Albumin, a marker of mature hepatocytes. Overexpression of Id3 in liver explants delayed the initiation of Albumin expression. Taken together, our observations show that Id3 is not only a positive regulator of hepatoblast proliferation, but also an inhibitor of their differentiation into hepatocytes in the developing chick liver. more...
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- 2006
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