免疫医科学分野

竹松 弘

タケマツ ヒロム  (Hiromu Takematsu)

基本情報

所属
藤田医科大学 医療科学部 医療検査学科 研究推進ユニット 分野教授
学位
博士(薬学)(1996年3月 京都大学)

J-GLOBAL ID
201401018385439878
researchmap会員ID
7000008580

外部リンク

論文

 83
  • Chizuru Akatsu, Yuko Naito-Matsui, Hajjaj H.M. Abdu-Allah, Akihiro Imamura, Wang Long, Hideharu Ishida, Hiromu Takematsu, Takeshi Tsubata
    Journal of Biological Chemistry 107630-107630 2024年8月  
  • Yuki Suganuma, Akihiro Imamura, Hiromune Ando, Makoto Kiso, Hiromu Takematsu, Takeshi Tsubata, Hideharu Ishida
    Glycoconjugate journal 40(2) 225-246 2023年4月  
    CD22, one of the sialic acid-binding immunoglobulin-like lectins (Siglecs), regulates B lymphocyte signaling via its interaction with glycan ligands bearing the sequence Neu5Ac/Gcα(2→6)Gal. We have developed the synthetic sialoside GSC-718 as a ligand mimic for CD22 and identified it as a potent CD22 inhibitor. Although the synthesis of CD22-binding sialosides including GSC-718 has been reported by our group, the synthetic route was unfortunately not suitable for large-scale synthesis. In this study, we developed an improved scalable synthetic procedure for sialosides which utilized 1,5-lactam formation as a key step. The improved procedure yielded sialosides incorporating a series of aglycones at the C2 position. Several derivatives with substituted benzyl residues as aglycones were found to bind to mouse CD22 with affinity comparable to that of GSC-718. The new procedure developed in this study affords sialosides in sufficient quantities for cell-based assays, and will facilitate the search for promising CD22 inhibitors that have therapeutic potential.
  • Masaru Takada, Daisuke Fukuhara, Toshihiko Takiura, Yukino Nishibori, Masashi Kotani, Zentaro Kiuchi, Akihiko Kudo, Olga Beltcheva, Noriko Ito-Nitta, Kazuhiro R Nitta, Toru Kimura, Jun-Ichi Suehiro, Tomohisa Katada, Hiromu Takematsu, Kunimasa Yan
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology 37(1) e22680 2023年1月  
    Spermatid production is a complex regulatory process in which coordination between hormonal control and apoptosis plays a pivotal role in maintaining a balanced number of sperm cells. Apoptosis in spermatogenesis is controlled by pro-apoptotic and anti-apoptotic molecules. Hormones involved in the apoptotic process during spermatogenesis include gonadotrophins, sex hormones, and glucocorticoid (GC). GC acts broadly as an apoptosis inducer by binding to its receptor (glucocorticoid receptor: GR) during organ development processes, such as spermatogenesis. However, the downstream pathway induced in GC-GR signaling and the apoptotic process during spermatogenesis remains poorly understood. We reported previously that GC induces full-length glucocorticoid-induced transcript 1 (GLCCI1-long), which functions as an anti-apoptotic mediator in thymic T cell development. Here, we demonstrate that mature murine testis expresses a novel isoform of GLCCI1 protein (GLCCI1-short) in addition to GLCCI1-long. We demonstrate that GLCCI1-long is expressed in spermatocytes along with GR. In contrast, GLCCI1-short is primarily expressed in spermatids where GR is absent; instead, the estrogen receptor is expressed. GLCCI1-short also binds to LC8, which is a known mediator of the anti-apoptotic effect of GLCCI1-long. A luciferase reporter assay revealed that β-estradiol treatment synergistically increased Glcci1-short promotor-driven luciferase activity in Erα-overexpressing cells. Together with the evidence that the conversion of testosterone to estrogen is preceded by aromatase expression in spermatids, we hypothesize that estrogen induces GLCCI1-short, which, in turn, may function as a novel anti-apoptotic mediator in mature murine testis.
  • Ichiro Hada, Akira Shimizu, Hiromu Takematsu, Yukino Nishibori, Toru Kimura, Toshiyuki Fukutomi, Akihiko Kudo, Noriko Ito-Nitta, Zentaro Kiuchi, Jaakko Patrakka, Naoaki Mikami, Simon Leclerc, Yoshihiro Akimoto, Yoshiaki Hirayama, Satoka Mori, Tomoko Takano, Kunimasa Yan
    Journal of the American Society of Nephrology : JASN 33(11) 2008-2025 2022年11月  
    BACKGROUND: The cause of podocyte injury in idiopathic nephrotic syndrome (INS) remains unknown. Although recent evidence points to the role of B cells and autoimmunity, the lack of animal models mediated by autoimmunity limits further research. We aimed to establish a mouse model mimicking human INS by immunizing mice with Crb2, a transmembrane protein expressed at the podocyte foot process. METHODS: C3H/HeN mice were immunized with the recombinant extracellular domain of mouse Crb2. Serum anti-Crb2 antibody, urine protein-to-creatinine ratio, and kidney histology were studied. For signaling studies, a Crb2-expressing mouse podocyte line was incubated with anti-Crb2 antibody. RESULTS: Serum anti-Crb2 autoantibodies and significant proteinuria were detected 4 weeks after the first immunization. The proteinuria reached nephrotic range at 9-13 weeks and persisted up to 29 weeks. Initial kidney histology resembled minimal change disease in humans, and immunofluorescence staining showed delicate punctate IgG staining in the glomerulus, which colocalized with Crb2 at the podocyte foot process. A subset of mice developed features resembling FSGS after 18 weeks. In glomeruli of immunized mice and in Crb2-expressing podocytes incubated with anti-Crb2 antibody, phosphorylation of ezrin, which connects Crb2 to the cytoskeleton, increased, accompanied by altered Crb2 localization and actin distribution. CONCLUSION: The results highlight the causative role of anti-Crb2 autoantibody in podocyte injury in mice. Crb2 immunization could be a useful model to study the immunologic pathogenesis of human INS, and may support the role of autoimmunity against podocyte proteins in INS.
  • Shohei Takahashi, Daisuke Fukuhara, Toru Kimura, Toshiyuki Fukutomi, Eriko Tanaka, Naoaki Mikami, Ichiro Hada, Hiromu Takematsu, Yukino Nishibori, Yoshihiro Akimoto, Hiroshi Kiyonari, Takaya Abe, Otmar Huber, Kunimasa Yan
    Biochemical and biophysical research communications 614 198-206 2022年7月23日  
    Podocyte damage is a major pathological lesion leading to focal segmental glomerulosclerosis (FSGS). Podocytes damaged by cellular stress undergo hypertrophy to compensate for podocytopenia. It is known that cyclin-dependent kinase inhibitors induced by p53 ensure podocytes hypertrophy; however, its precise mechanism remains to be further investigated. In this study, we found that ubiquitin specific protease 40 (USP40) is a novel regulator of p53. Although USP40 knockout mice established in the present study revealed no abnormal kidney phenotype, intermediate filament Nestin was upregulated in the glomeruli, and was bound to and colocalized with USP40. We also found that USP40 deubiquitinated histidine triad nucleotide-binding protein 1 (HINT1), an inducer of p53. Gene knockdown experiments of USP40 in cultured podocytes revealed the reduction of HINT1 and p53 protein expression. Finally, in glomerular podocytes of mouse FSGS, upregulation of HINT1 occurred in advance of the proteinuria, which was followed by upregulation of USP40, p53 and Nestin. In conclusion, USP40 bound to Nestin deubiquitinates HINT1, and in consequence upregulates p53. These results provide additional insight into the pathological mechanism of podocyte hypertrophy in FSGS.

MISC

 54
  • Cindy M. Spruit, Nikoloz Nemanichvili, Masatoshi Okamatsu, Hiromu Takematsu, Geert-Jan Boons, Robert P. de Vries
    Viruses 13(5) 815-815 2021年5月1日  査読有り
    The first step in influenza virus infection is the binding of hemagglutinin to sialic acid-containing glycans present on the cell surface. Over 50 different sialic acid modifications are known, of which N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) are the two main species. Animal models with α2,6 linked Neu5Ac in the upper respiratory tract, similar to humans, are preferred to enable and mimic infection with unadapted human influenza A viruses. Animal models that are currently most often used to study human influenza are mice and ferrets. Additionally, guinea pigs, cotton rats, Syrian hamsters, tree shrews, domestic swine, and non-human primates (macaques and marmosets) are discussed. The presence of NeuGc and the distribution of sialic acid linkages in the most commonly used models is summarized and experimentally determined. We also evaluated the role of Neu5Gc in infection using Neu5Gc binding viruses and cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH)−/− knockout mice, which lack Neu5Gc and concluded that Neu5Gc is unlikely to be a decoy receptor. This article provides a base for choosing an appropriate animal model. Although mice are one of the most favored models, they are hardly naturally susceptible to infection with human influenza viruses, possibly because they express mainly α2,3 linked sialic acids with both Neu5Ac and Neu5Gc modifications. We suggest using ferrets, which resemble humans closely in the sialic acid content, both in the linkages and the lack of Neu5Gc, lung organization, susceptibility, and disease pathogenesis.
  • 佐藤 弓奈, 中島, 英規 Laine Roger, A, 岡, 昌吾, 竹松
    日本生化学会大会プログラム・講演要旨集 91回(1P) 367 2018年9月  
  • 井谷 有希, 渡邉 寛, 岡 昌吾, 竹松 弘
    日本生化学会大会プログラム・講演要旨集 91回(1T14e) 363 2018年9月  
  • Morise J, Takematsu H, Oka S
    Biochimica et biophysica acta 1861(10) 2455-2461 2017年10月  査読有り
  • 森瀬 譲二, 鈴木 健一, 北川 英佳, 若園 佳彦, 高宮 考悟, 楠見 明弘, 竹松 弘, 岡 昌吾
    日本生化学会大会プログラム・講演要旨集 89回 [1P-306] 2016年9月  

共同研究・競争的資金等の研究課題

 11

その他

 1
  • ヒト型シアル酸を持つノックアウトマウス