Institution
Japan Agency for Medical Research and Development
Facility•Tokyo, Japan•
About: Japan Agency for Medical Research and Development is a facility organization based out in Tokyo, Japan. It is known for research contribution in the topics: Immune system & Receptor. The organization has 544 authors who have published 907 publications receiving 21295 citations. The organization is also known as: AMED.
Topics: Immune system, Receptor, Inflammation, Cancer, Gene
Papers
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TL;DR: This Review aims to provide a comprehensive understanding of the role of SREBPs in physiology and pathophysiology at the cell, organ and organism levels.
Abstract: Cellular lipid metabolism and homeostasis are controlled by sterol regulatory-element binding proteins (SREBPs). In addition to performing canonical functions in the transcriptional regulation of genes involved in the biosynthesis and uptake of lipids, genome-wide system analyses have revealed that these versatile transcription factors act as important nodes of convergence and divergence within biological signalling networks. Thus, they are involved in myriad physiological and pathophysiological processes, highlighting the importance of lipid metabolism in biology. Changes in cell metabolism and growth are reciprocally linked through SREBPs. Anabolic and growth signalling pathways branch off and connect to multiple steps of SREBP activation and form complex regulatory networks. In addition, SREBPs are implicated in numerous pathogenic processes such as endoplasmic reticulum stress, inflammation, autophagy and apoptosis, and in this way, they contribute to obesity, dyslipidaemia, diabetes mellitus, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, chronic kidney disease, neurodegenerative diseases and cancers. This Review aims to provide a comprehensive understanding of the role of SREBPs in physiology and pathophysiology at the cell, organ and organism levels.
575 citations
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TL;DR: A protocol for advanced CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis) is described in this paper, which enables simple and efficient organ clearing, rapid imaging by light-sheet microscopy and quantitative imaging analysis of multiple samples.
Abstract: Here we describe a protocol for advanced CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis). The CUBIC protocol enables simple and efficient organ clearing, rapid imaging by light-sheet microscopy and quantitative imaging analysis of multiple samples. The organ or body is cleared by immersion for 1-14 d, with the exact time required dependent on the sample type and the experimental purposes. A single imaging set can be completed in 30-60 min. Image processing and analysis can take <1 d, but it is dependent on the number of samples in the data set. The CUBIC clearing protocol can process multiple samples simultaneously. We previously used CUBIC to image whole-brain neural activities at single-cell resolution using Arc-dVenus transgenic (Tg) mice. CUBIC informatics calculated the Venus signal subtraction, comparing different brains at a whole-organ scale. These protocols provide a platform for organism-level systems biology by comprehensively detecting cells in a whole organ or body.
554 citations
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TL;DR: A comprehensive concept that connects NAD+ metabolism to the control of aging and longevity in mammals has been proposed, and the stage is now set to test whether these exciting preclinical results can be translated to improve human health.
528 citations
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TL;DR: Results indicate that exosome secretion maintains cellular homeostasis by removing harmful cytoplasmic DNA from cells, and provide valuable new insights into the control of cellularHomeostasis.
Abstract: Emerging evidence is revealing that exosomes contribute to many aspects of physiology and disease through intercellular communication However, the biological roles of exosome secretion in exosome-secreting cells have remained largely unexplored Here we show that exosome secretion plays a crucial role in maintaining cellular homeostasis in exosome-secreting cells The inhibition of exosome secretion results in the accumulation of nuclear DNA in the cytoplasm, thereby causing the activation of cytoplasmic DNA sensing machinery This event provokes the innate immune response, leading to reactive oxygen species (ROS)-dependent DNA damage response and thus induce senescence-like cell-cycle arrest or apoptosis in normal human cells These results, in conjunction with observations that exosomes contain various lengths of chromosomal DNA fragments, indicate that exosome secretion maintains cellular homeostasis by removing harmful cytoplasmic DNA from cells Together, these findings enhance our understanding of exosome biology, and provide valuable new insights into the control of cellular homeostasis
527 citations
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TL;DR: The aim of this study was to investigate whether altered composition of human intestinal microbiota in RA patients contributes to the development of arthritis.
Abstract: Objective
The intestinal microbiota is involved in the pathogenesis of arthritis. Altered microbiota composition has been demonstrated in patients with rheumatoid arthritis (RA). However, it remains unclear how dysbiosis contributes to the development of arthritis. The aim of this study was to investigate whether altered composition of human intestinal microbiota in RA patients contributes to the development of arthritis.
Methods
We analyzed the fecal microbiota of patients with early RA and healthy controls, using 16S ribosomal RNA−based deep sequencing. We inoculated fecal samples from RA patients and healthy controls into germ-free arthritis-prone SKG mice and evaluated the immune responses. We also analyzed whether the lymphocytes of SKG mice harboring microbiota from RA patients react with the arthritis-related autoantigen 60S ribosomal protein L23a (RPL23A).
Results
A subpopulation of patients with early RA harbored intestinal microbiota dominated by Prevotella copri; SKG mice harboring microbiota from RA patients had an increased number of intestinal Th17 cells and developed severe arthritis when treated with zymosan. Lymphocytes in regional lymph nodes and the colon, but not the spleen, of these mice showed enhanced interleukin-17 (IL-17) responses to RPL23A. Naive SKG mouse T cells cocultured with P copri−stimulated dendritic cells produced IL-17 in response to RPL23A and rapidly induced arthritis.
Conclusion
We demonstrated that dysbiosis increases sensitivity to arthritis via activation of autoreactive T cells in the intestine. Autoreactive SKG mouse T cells are activated by dysbiotic microbiota in the intestine, causing joint inflammation. Dysbiosis is an environmental factor that triggers arthritis development in genetically susceptible mice.
428 citations
Authors
Showing all 545 results
Name | H-index | Papers | Citations |
---|---|---|---|
Shuh Narumiya | 137 | 595 | 70183 |
Kozo Kaibuchi | 129 | 493 | 60461 |
Kiyoshi Takeda | 129 | 416 | 109817 |
Kouji Matsushima | 124 | 590 | 56995 |
Akihiko Yoshimura | 117 | 514 | 50270 |
Osamu Takeuchi | 116 | 288 | 90116 |
Shimon Sakaguchi | 115 | 379 | 88763 |
Eisuke Nishida | 112 | 349 | 45918 |
Minoru Yoshida | 111 | 783 | 55767 |
Hiroyuki Aburatani | 110 | 699 | 59178 |
Hiroyuki Arai | 108 | 891 | 50820 |
Issei Komuro | 101 | 1266 | 46138 |
Yoshihiro Ogawa | 100 | 647 | 40069 |
Hiroshi Kiyono | 98 | 644 | 34181 |
Haruhiko Koseki | 97 | 412 | 40663 |