分子病態治療研究センター 人類遺伝学研究部
  1. 研究者リスト
  2. 松村 貴由

松村 貴由

マツムラ タカヨシ  (Takayoshi Matsumura)

基本情報

所属
自治医科大学 分子病態治療研究センター　人類遺伝学研究部 教授
研究者番号
80436485
J-GLOBAL ID
202101014043069173
researchmap会員ID
R000016874

論文

 26
  • Naoya Yamada, Tadayoshi Karasawa, Junya Ito, Daisuke Yamamuro, Kazushi Morimoto, Toshitaka Nakamura, Takanori Komada, Chintogtokh Baatarjav, Yuma Saimoto, Yuka Jinnouchi, Kazuhisa Watanabe, Kouichi Miura, Naoya Yahagi, Kiyotaka Nakagawa, Takayoshi Matsumura, Ken-Ichi Yamada, Shun Ishibashi, Naohiro Sata, Marcus Conrad, Masafumi Takahashi
    Nature communications 15(1) 2195-2195 2024年3月12日  
    Recent evidence indicates ferroptosis is implicated in the pathophysiology of various liver diseases; however, the organ-specific regulation mechanism is poorly understood. Here, we demonstrate 7-dehydrocholesterol reductase (DHCR7), the terminal enzyme of cholesterol biosynthesis, as a regulator of ferroptosis in hepatocytes. Genetic and pharmacological inhibition (with AY9944) of DHCR7 suppress ferroptosis in human hepatocellular carcinoma Huh-7 cells. DHCR7 inhibition increases its substrate, 7-dehydrocholesterol (7-DHC). Furthermore, exogenous 7-DHC supplementation using hydroxypropyl β-cyclodextrin suppresses ferroptosis. A 7-DHC-derived oxysterol metabolite, 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), is increased by the ferroptosis-inducer RSL-3 in DHCR7-deficient cells, suggesting that the ferroptosis-suppressive effect of DHCR7 inhibition is associated with the oxidation of 7-DHC. Electron spin resonance analysis reveals that 7-DHC functions as a radical trapping agent, thus protecting cells from ferroptosis. We further show that AY9944 inhibits hepatic ischemia-reperfusion injury, and genetic ablation of Dhcr7 prevents acetaminophen-induced acute liver failure in mice. These findings provide new insights into the regulatory mechanism of liver ferroptosis and suggest a potential therapeutic option for ferroptosis-related liver diseases.
  • Tadayoshi Karasawa, Takanori Komada, Chintogtokh Baatarjav, Emi Aizawa, Yoshiko Mizushina, Kenta Fujimura, Yoshitaka Gunji, Satoko Komori, Hidetoshi Aizawa, Cantona Billton Jing Tao, Takayoshi Matsumura, Masafumi Takahashi
    Biochemical and biophysical research communications 686 149158-149158 2023年12月17日  
    Caspase-11 is an inflammatory caspase that triggers an inflammatory response by regulating non-canonical NLRP3 inflammasome activation. Although the deficiency of both caspase-11 and caspase-1, another inflammatory caspase that functions as an executor of the inflammasome, prevents the development of atherosclerosis, the effect of caspase-11 deficiency alone on the development of atherosclerosis has not been fully evaluated. In the present study, we found that caspase-11 deficiency prevented the formation of the necrotic core, whereas it did not affect the development of atherosclerosis in Apoe-deficient mice. Notably, the infiltration of neutrophils into atherosclerotic lesions was attenuated by caspase-11 deficiency. RNA-seq analysis of stage-dependent expression of atherosclerotic lesions revealed that both upregulations of caspase-11 and neutrophil migration are common features of advanced atherosclerotic lesions. Furthermore, similar expression profiles were observed in unstable human plaque. These data suggest that caspase-11 regulates neutrophil recruitment and plaque destabilization in advanced atherosclerotic lesions.
  • Kenta Fujimura, Tadayoshi Karasawa, Takanori Komada, Naoya Yamada, Yoshiko Mizushina, Chintogtokh Baatarjav, Takayoshi Matsumura, Kinya Otsu, Norihiko Takeda, Hiroaki Mizukami, Kazuomi Kario, Masafumi Takahashi
    Journal of molecular and cellular cardiology 180 58-68 2023年7月  
    Sepsis is a life-threatening syndrome, and its associated mortality is increased when cardiac dysfunction and damage (septic cardiomyopathy [SCM]) occur. Although inflammation is involved in the pathophysiology of SCM, the mechanism of how inflammation induces SCM in vivo has remained obscure. NLRP3 inflammasome is a critical component of the innate immune system that activates caspase-1 (Casp1) and causes the maturation of IL-1β and IL-18 as well as the processing of gasdermin D (GSDMD). Here, we investigated the role of the NLRP3 inflammasome in a murine model of lipopolysaccharide (LPS)-induced SCM. LPS injection induced cardiac dysfunction, damage, and lethality, which was significantly prevented in NLRP3-/- mice, compared to wild-type (WT) mice. LPS injection upregulated mRNA levels of inflammatory cytokines (Il6, Tnfa, and Ifng) in the heart, liver, and spleen of WT mice, and this upregulation was prevented in NLRP3-/- mice. LPS injection increased plasma levels of inflammatory cytokines (IL-1β, IL-18, and TNF-α) in WT mice, and this increase was markedly inhibited in NLRP3-/- mice. LPS-induced SCM was also prevented in Casp1/11-/- mice, but not in Casp11mt, IL-1β-/-, IL-1α-/-, or GSDMD-/- mice. Notably, LPS-induced SCM was apparently prevented in IL-1β-/- mice transduced with adeno-associated virus vector expressing IL-18 binding protein (IL-18BP). Furthermore, splenectomy, irradiation, or macrophage depletion alleviated LPS-induced SCM. Our findings demonstrate that the cross-regulation of NLRP3 inflammasome-driven IL-1β and IL-18 contributes to the pathophysiology of SCM and provide new insights into the mechanism underlying the pathogenesis of SCM.
  • Takayoshi Matsumura, Haruhito Totani, Yoshitaka Gunji, Masahiro Fukuda, Rui Yokomori, Jianwen Deng, Malini Rethnam, Chong Yang, Tze King Tan, Tadayoshi Karasawa, Kazuomi Kario, Masafumi Takahashi, Motomi Osato, Takaomi Sanda, Toshio Suda
    Nature Communications 13(1) 7064-7064 2022年11月18日  筆頭著者責任著者
    Abstract The transcription factor MYB is a crucial regulator of hematopoietic stem and progenitor cells. However, the nature of lineage-specific enhancer usage of the Myb gene is largely unknown. We identify the Myb −68 enhancer, a regulatory element which marks basophils and mast cells. Using the Myb −68 enhancer activity, we show a population of granulocyte-macrophage progenitors with higher potential to differentiate into basophils and mast cells. Single cell RNA-seq demonstrates the differentiation trajectory is continuous from progenitors to mature basophils in vivo, characterizes bone marrow cells with a gene signature of mast cells, and identifies LILRB4 as a surface marker of basophil maturation. Together, our study leads to a better understanding of how MYB expression is regulated in a lineage-associated manner, and also shows how a combination of lineage-related reporter mice and single-cell transcriptomics can overcome the rarity of target cells and enhance our understanding of gene expression programs that control cell differentiation in vivo.
  • Chintogtokh Baatarjav, Takanori Komada, Tadayoshi Karasawa, Naoya Yamada, Ariunaa Sampilvanjil, Takayoshi Matsumura, Masafumi Takahashi
    Cell Death & Differentiation 2022年6月23日  
もっとみる

MISC

 5
  • 大里 元美, Ong Kelly Ooi Kee, Mok Michelle Meng Huang, 横溝 智雅, 松村 貴由, 須田 年生, 麻生 範雄, Koeffler Phillip, Tenen Daniel G., 清水 律子, 山本 雅之, 伊藤 嘉明, Yeoh Allen Eng-Juh, Chng Wee Joo
    臨床血液 59(9) 1700-1700 2018年9月  
  • Ayako Nakamura-Ishizu, Takayoshi Matsumura, Terumasa Umemoto, A'Qilah Abdul Majeed, Toshio Suda
    EXPERIMENTAL HEMATOLOGY 44(9) S91-S91 2016年9月  
  • Chikashi Terao, Hajime Yoshifuji, Akinori Kimura, Takayoshi Matsumura, Koichiro Ohmura, Meiko Takahashi, Masakazu Shimizu, Takahisa Kawaguchi, Zhiyong Chen, Taeko K. Naruse, Aiko Sato-Otsubo, Yusuke Ebana, Yasuhiro Maejima, Hideyuki Kinoshita, Kosaku Murakami, Daisuke Kawabata, Yoko Wada, Ichiei Narita, Junichi Tazaki, Yasushi Kawaguchi, Hisashi Yamanaka, Kimiko Yurugi, Yasuo Miura, Taira Maekawa, Seishi Ogawa, Issei Komuro, Ryozo Nagai, Ryo Yamada, Yasuharu Tabara, Mitsuaki Isobe, Tsuneyo Mimori, Fumihiko Matsuda
    American Journal of Human Genetics 93(2) 289-297 2013年8月8日  
    Takayasu arteritis (TAK) is an autoimmune systemic vasculitis of unknown etiology. Although previous studies have revealed that HLA-B*52:01 has an effect on TAK susceptibility, no other genetic determinants have been established so far. Here, we performed genome scanning of 167 TAK cases and 663 healthy controls via Illumina Infinium Human Exome BeadChip arrays, followed by a replication study consisting of 212 TAK cases and 1,322 controls. As a result, we found that the IL12B region on chromosome 5 (rs6871626, overall p = 1.7 × 10-13, OR = 1.75, 95% CI 1.42-2.16) and the MLX region on chromosome 17 (rs665268, overall p = 5.2 × 10-7, OR = 1.50, 95% CI 1.28-1.76) as well as the HLA-B region (rs9263739, a proxy of HLA-B*52:01, overall p = 2.8 × 10-21, OR = 2.44, 95% CI 2.03-2.93) exhibited significant associations. A significant synergistic effect of rs6871626 and rs9263739 was found with a relative excess risk of 3.45, attributable proportion of 0.58, and synergy index of 3.24 (p ≤ 0.00028) in addition to a suggestive synergistic effect between rs665268 and rs926379 (p ≤ 0.027). We also found that rs6871626 showed a significant association with clinical manifestations of TAK, including increased risk and severity of aortic regurgitation, a representative severe complication of TAK. Detection of these susceptibility loci will provide new insights to the basic mechanisms of TAK pathogenesis. Our findings indicate that IL12B plays a fundamental role on the pathophysiology of TAK in combination with HLA-B*52:01 and that common autoimmune mechanisms underlie the pathology of TAK and other autoimmune disorders such as psoriasis and inflammatory bowel diseases in which IL12B is involved as a genetic predisposing factor. © 2013 The American Society of Human Genetics.
  • Toru Suzuki, Kenichi Aizawa, Takayoshi Matsumura, Ryozo Nagai
    Arteriosclerosis, thrombosis, and vascular biology 25(6) 1135-41 2005年6月  査読有り
    The Krüppel-like factor (KLF) family is a recently highlighted group of zinc finger transcription factors given their important biological roles which include the vasculature. KLF2, KLF4, KLF5, and KLF6 are notable factors that have been implicated in developmental as well as pathological vascular processes. In this brief review, we provide an up-to-date summary of the physiological functions and cellular effects as well as transcriptional regulatory mechanisms of the vascular KLFs. Through such, we aim to provide a working view for understanding the pathological actions of KLFs in the vasculature.
  • Toru Suzuki, Takayoshi Matsumura, Ryozo Nagai
    Trends in cardiovascular medicine 15(4) 125-9 2005年5月  査読有り
    Transcriptional regulation in eukaryotes requires an understanding of the regulation of the chromatin structure. Chromatin is the eukaryotic-specific packaging/compaction of DNA with nucleosomal histones. This present review discusses recent advancements made in the field of chromatin-associated transcriptional regulation and their implications to the cardiovasculature.

共同研究・競争的資金等の研究課題

 4
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