Updated on 2025/10/23

写真a

 
WANG Dengli
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Assistant Professor
Position
Assistant Professor
Contact information
メールアドレス
External link

Degree

  • PhD. ( 2017.9   Okayama University )

Research Interests

  • Intracerebral Hemorrhage

  • Inflammation

  • anti-HMGB1 antibody

Research Areas

  • Life Science / Pharmacology  / 脳出血 HMGB1 抗体

  • Life Science / Pharmacology  / ribonucleoprotein, drug discovery

Education

  • Okayama University   大学院医歯薬学総合研究科  

    2014.10 - 2017.9

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    Country: Japan

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  • Jilin University    

    2010.8 - 2013.12

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    Country: China

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  • Changchun University of Chinese Medicine    

    2006.8 - 2010.8

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Research History

  • Okayama University   Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences   Assistant Professor

    2021.4

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  • Okayama University   Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences   Assistant Professor

    2017.10 - 2021.3

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Professional Memberships

 

Papers

  • Anti-HMGB1 Antibody Therapy Ameliorates Spinal Cord Ischemia-Reperfusion Injury in Rabbits. International journal

    Genya Muraoka, Yasuhiro Fujii, Keyue Liu, Handong Qiao, Dengli Wang, Daiki Ousaka, Susumu Oozawa, Shingo Kasahara, Masahiro Nishibori

    International journal of molecular sciences   26 ( 17 )   2025.9

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    Spinal cord ischemia-reperfusion (SCI/R) injury remains a major clinical challenge with limited therapeutic options. High-mobility group box 1 (HMGB1), a proinflammatory mediator released during cellular stress, has been implicated in the pathogenesis of ischemia-reperfusion-induced neural damage. In this study, we investigated the neuroprotective potential of the anti-HMGB1 monoclonal antibody (mAb) in a rabbit model of SCI/R injury. Male New Zealand White rabbits were anesthetized and subjected to 11 min of abdominal aortic occlusion using a micro-bulldog clamp following heparinization. Anti-HMGB1 mAb or control IgG was administered intravenously immediately after reperfusion and again at 6 h post-reperfusion. Neurological function was assessed at 6, 24, and 48 h after reperfusion using the modified Tarlov scoring system. The rabbits were euthanized 48 h after reperfusion for spinal cord and blood sampling. Treatment with anti-HMGB1 mAb significantly improved neurological outcomes, reduced the extent of spinal cord infarction, preserved motor neuron viability, and decreased the presence of activated microglia and infiltrating neutrophils. Furthermore, it attenuated apoptosis, oxidative stress, and inflammatory responses in the spinal cord, and helped maintain the integrity of the blood-spinal cord barrier. These findings suggest that anti-HMGB1 mAb may serve as a promising therapeutic agent for SCI/R injury.

    DOI: 10.3390/ijms26178643

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  • Antithrombin regulates neutrophil activities through the stimulation of C-type lectin family 1A Reviewed

    Yohei Takahashi, Soe Soe Htwe, Dengli Wang, Hidenori Wake, Mariko Yata, Nahoko Tomonobu, Rie Kinoshita, Masakiyo Sakaguchi, Masahiro Nishibori

    Blood Vessels, Thrombosis & Hemostasis   2025.2

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    DOI: 10.1016/j.bvth.2024.100032

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  • Glucocorticoids induce HMGB1 release in primary cultured rat cortical microglia International journal

    Kazue Hisaoka-Nakashima, Yuka Takeuchi, Yukino Saito, Takahisa Shimoda, Yoki Nakamura, Dengli Wang, Keyue Liu, Masahiro Nishibori, Norimitsu Morioka

    Neuroscience   560   56 - 66   2024.11

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    Stress, a risk factor for major depressive disorder and Alzheimer disease, leads to the release of high-mobility group box-1 (HMGB1) protein, which in turn causes neuroinflammation. The mechanism underlying stress-induced HMGB1 release is unknown, but stress-associated glucocorticoids could be involved. Primary cultured rat cortical microglia and neurons were treated with corticosterone, a stress-associated glucocorticoid, and HMGB1 release was measured by ELISA and western blotting to test this hypothesis. With corticosterone treatment, significant HMGB1 was released in microglia but not in neuronal cell cultures. HMGB1 mRNA expression and HMGB1 protein expression in microglia were not affected by corticosterone treatment. Thus, the source of extracellular HMGB1 released into the medium is likely to be existing nuclear HMGB1 rather than newly synthesized HMGB1. Corticosterone-induced HMGB1 release in microglia culture was significantly attenuated by blocking glucocorticoid receptors but not mineralocorticoid receptors. Dexamethasone, a selective glucocorticoid receptor agonist, and dexamethasone-bovine serum albumin (BSA), a membrane-impermeable glucocorticoid receptor agonist used to confirm the membrane receptor-mediated effects of glucocorticoids, increased the release of HMGB1. Immunocytochemistry showed that HMGB1 translocated from the nucleus to the cytoplasm following dexamethasone or dexamethasone-BSA treatment through glucocorticoid receptors. The present findings suggest that glucocorticoids stimulate microglial membrane glucocorticoid receptors and trigger cytoplasmic translocation and extracellular release of nuclear HMGB1. Thus, under stress conditions, glucocorticoids induce microglial HMGB1 release, leading to a neuroinflammatory state that could mediate neurological disorders.

    DOI: 10.1016/j.neuroscience.2024.09.031

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  • Anti-HMGB1 mAb Therapy Reduces Epidural Hematoma Injury. International journal

    Shangze Gao, Dengli Wang, Keyue Liu, Yasuko Tomono, Li Fu, Yuan Gao, Yohei Takahashi, Mariko Yata, Masahiro Nishibori

    International journal of molecular sciences   25 ( 11 )   2024.5

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    Epidural and subdural hematomas are commonly associated with traumatic brain injury. While surgical removal is the primary intervention for these hematomas, it is also critical to prevent and reduce complications such as post-traumatic epilepsy, which may result from inflammatory responses in the injured brain areas. In the present study, we observed that high mobility group box-1 (HMGB1) decreased in the injured brain area beneath the epidural hematoma (EDH) in rats, concurrent with elevated plasma levels of HMGB1. Anti-HMGB1 monoclonal antibody therapy strongly inhibited both HMGB1 release and the subsequent increase in plasma levels. Moreover, this treatment suppressed the up-regulation of inflammatory cytokines and related molecules such as interleukin-1-beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) in the injured areas. Our in vitro experiments using SH-SY5Y demonstrated that hematoma components-thrombin, heme, and ferrous ion- prompted HMGB1 translocation from the nuclei to the cytoplasm, a process inhibited by the addition of the anti-HMGB1 mAb. These findings suggest that anti-HMGB1 mAb treatment not only inhibits HMGB1 translocation but also curtails inflammation in injured areas, thereby protecting the neural tissue. Thus, anti-HMGB1 mAb therapy could serve as a complementary therapy for an EDH before/after surgery.

    DOI: 10.3390/ijms25115889

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  • Perineural Treatment with High Mobility Group Box-1 Monoclonal Antibody Prevents Initiation of Pain-Like Behaviors in Female Mice with Trigeminal Neuropathy

    Simeng Ma, Yoki Nakamura, Takahiro Kochi, Suzuna Uemoto, Kazue Hisaoka-Nakashima, Dengli Wang, Keyue Liu, Hidenori Wake, Masahiro Nishibori, Norimitsu Morioka

    Biological and Pharmaceutical Bulletin   47 ( 1 )   221 - 226   2024.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Pharmaceutical Society of Japan  

    Post-traumatic trigeminal neuropathy (PTTN) is a type of chronic pain caused by damage to the trigeminal nerve. A previous study reported that pretreatment with anti-high mobility group box-1 (HMGB1) neutralizing antibodies (nAb) prevented the onset of PTTN following distal infraorbital nerve chronic constriction injury (dIoN-CCI) in male mice. Clinical evidence indicates a high incidence of PTTN in females. Although our previous study found that perineural HMGB1 is crucial in initiation of PTTN in male mice, it is currently unknown whether HMGB1 is also involved in the pathogenesis of PTTN in female mice. Therefore, in the current study, we examined the effect of anti-HMGB1 nAb on pain-like behavior in female mice following dIoN-CCI surgery. We found that dIoN-CCI surgery enhanced reactivity to mechanical and cold stimuli in female mice, which was suppressed by treatment with anti-HMGB1 nAb. Moreover, the increase in macrophages after dIoN-CCI was significantly attenuated by pretreatment with anti-HMGB1 nAb. Furthermore, anti-HMGB1 nAb treatment inhibited microglial activation in the trigeminal spinal tract nucleus. These data suggest that HMGB1 also plays a crucial role in the onset of PTTN after nerve injury in female mice. Thus, anti-HMGB1 nAb could be a novel therapeutic agent for inhibiting the onset of PTTN in female and male mice.

    DOI: 10.1248/bpb.b23-00729

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  • Protective effects of an anti-4-HNE monoclonal antibody against liver injury and lethality of endotoxemia in mice

    Handong Qiao, Yuta Morioka, Dengli Wang, Keyue Liu, Shangze Gao, Hidenori Wake, Daiki Ousaka, Kiyoshi Teshigawara, Shuji Mori, Masahiro Nishibori

    European Journal of Pharmacology   950   175702 - 175702   2023.7

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    DOI: 10.1016/j.ejphar.2023.175702

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  • 非小細胞肺癌の微小環境におけるHigh Mobility Group Box-1 protein(HMGB1)の役割

    伊達 慶一, 諏澤 憲, 吉川 真生, 大亀 正義, 土生 智大, 岩田 一馬, 松田 直樹, Yin Min Thu, 枝園 和彦, 山本 寛斉, 岡崎 幹生, 王 登莉, 逢坂 大樹, 細野 祥之, 豊岡 伸一

    日本外科学会定期学術集会抄録集   123回   SF - 6   2023.4

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    Language:Japanese   Publisher:(一社)日本外科学会  

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  • Histamine induced high mobility group box-1 release from vascular endothelial cells through H-1 receptor

    Shangze Gao, Keyue Liu, Wenhan Ku, Dengli Wang, Hidenori Wake, Handong Qiao, Kiyoshi Teshigawara, Masahiro Nishibori

    FRONTIERS IN IMMUNOLOGY   13   2022.10

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    DOI: 10.3389/fimmu.2022.930683

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  • Treatment of Marmoset Intracerebral Hemorrhage with Humanized Anti-HMGB1 mAb

    Dengli Wang, Daiki Ousaka, Handong Qiao, Ziyi Wang, Kun Zhao, Shangze Gao, Keyue Liu, Kiyoshi Teshigawara, Kenzo Takada, Masahiro Nishibori

    CELLS   11 ( 19 )   2022.10

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    DOI: 10.3390/cells11192970

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  • High-mobility group box 1-mediated hippocampal microglial activation induces cognitive impairment in mice with neuropathic pain

    Kazue Hisaoka-Nakashima, Kazuto Ohata, Natsuki Yoshimoto, Shintarou Tokuda, Nanako Yoshii, Yoki Nakamura, Dengli Wang, Keyue Liu, Hidenori Wake, Takayuki Yoshida, Yukio Ago, Kouichi Hashimoto, Masahiro Nishibori, Norimitsu Morioka

    Experimental Neurology   355   114146 - 114146   2022.9

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    DOI: 10.1016/j.expneurol.2022.114146

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  • Development of hepatic impairment aggravates chemotherapy-induced peripheral neuropathy following oxaliplatin treatment: Evidence from clinical and preclinical studies.

    Tomoyoshi Miyamoto, Risa Domoto, Fumiko Sekiguchi, Riki Kamaguchi, Rika Nishimura, Misato Matsuno, Maho Tsubota, Masanori Fujitani, Shigekatsu Hatanaka, Yuichi Koizumi, Dengli Wang, Masahiro Nishibori, Atsufumi Kawabata

    Journal of pharmacological sciences   148 ( 3 )   315 - 325   2022.3

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    DOI: 10.1016/j.jphs.2022.01.006

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  • Targeting necroptosis in muscle fibers ameliorates inflammatory myopathies

    Mari Kamiya, Fumitaka Mizoguchi, Kimito Kawahata, Dengli Wang, Masahiro Nishibori, Jessica Day, Cynthia Louis, Ian P. Wicks, Hitoshi Kohsaka, Shinsuke Yasuda

    NATURE COMMUNICATIONS   13 ( 1 )   2022.1

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    DOI: 10.1038/s41467-021-27875-4

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  • Central high mobility group box-1 induces mechanical hypersensitivity with spinal microglial activation in a mouse model of hemi-Parkinson’s disease

    Fumiaki Sato, Yoki Nakamura, Simeng Ma, Takahiro Kochi, Kazue Hisaoka-Nakashima, Dengli Wang, Keyue Liu, Hidenori Wake, Masahiro Nishibori, Norimitsu Morioka

    Biomedicine & Pharmacotherapy   145   112479 - 112479   2022.1

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    DOI: 10.1016/j.biopha.2021.112479

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  • Role of neuron-derived ATP in paclitaxel-induced HMGB1 release from macrophages and peripheral neuropathy.

    Risa Domoto, Fumiko Sekiguchi, Riki Kamaguchi, Maiko Iemura, Hiroki Yamanishi, Maho Tsubota, Dengli Wang, Masahiro Nishibori, Atsufumi Kawabata

    Journal of pharmacological sciences   148 ( 1 )   156 - 161   2022.1

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    DOI: 10.1016/j.jphs.2021.11.003

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  • A new approach to combat the sepsis including COVID-19 by accelerating detoxification of hemolysis-related DAMPs

    Ousaka Daiki, Wang Dengli, Nishiboli Masahiro

    Proceedings for Annual Meeting of The Japanese Pharmacological Society   95   1-S03-1   2022

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    Sepsis is one of the leading cause of death worldwide. Recently, several studies suggested that free-hemoglobin and heme derived from hemolysis are important factors which may be associated with severity of septic patients including COVID-19. In other words, hemolysis-derived products enhance the inflammatory responses as damage-associated molecular patterns (DAMPs) in both intravascular and extravascular space. In addition, hemoglobin has vasoconstrictive activity by depleting nitric oxide, whereas heme or Fe2+ produce reactive oxygen species (ROS) through Fenton reaction leading to tissue injury. At present, we have no therapeutic options against sepsis-related hemolysis in clinical settings, however, there are might be two therapeutic strategies in this regard. One is supplemental therapy of depleted scavenging proteins such as haptoglobin and hemopexin, the other is activation of the internal scavenging system including macrophage-CD163 pathway. These novel targets against sepsis are also critical for the next pandemic. We will show you our recent data aiming at anti-hemolytic therapy.

    DOI: 10.1254/jpssuppl.95.0_1-s03-1

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  • Combinatrial treatment of anti-High Mobility Group Box-1 monoclonal antibody and epothilone B improves functional recovery after spinal cord contusion injury. International journal

    Yicheng Zhu, Naohiro Uezono, Tetsuro Yasui, Masahide Nakajo, Tatsuya Nagai, Dengli Wang, Masahiro Nishibori, Kinichi Nakashima

    Neuroscience research   172   13 - 25   2021.11

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    DOI: 10.1016/j.neures.2021.04.002

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  • Neuroprotective Effects of Anti-high Mobility Group Box-1 Monoclonal Antibody Against Methamphetamine-Induced Dopaminergic Neurotoxicity. International journal

    Kaori Masai, Keita Kuroda, Nami Isooka, Ryo Kikuoka, Shinki Murakami, Sunao Kamimai, Dengli Wang, Keyue Liu, Ikuko Miyazaki, Masahiro Nishibori, Masato Asanuma

    Neurotoxicity research   39 ( 5 )   1511 - 1523   2021.10

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    DOI: 10.1007/s12640-021-00402-5

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  • Caspase-Dependent HMGB1 Release from Macrophages Participates in Peripheral Neuropathy Caused by Bortezomib, a Proteasome-Inhibiting Chemotherapeutic Agent, in Mice. International journal

    Maho Tsubota, Takaya Miyazaki, Yuya Ikeda, Yusuke Hayashi, Yui Aokiba, Shiori Tomita, Fumiko Sekiguchi, Dengli Wang, Masahiro Nishibori, Atsufumi Kawabata

    Cells   10 ( 10 )   2021.9

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    DOI: 10.3390/cells10102550

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  • Pretreatment with High Mobility Group Box-1 Monoclonal Antibody Prevents the Onset of Trigeminal Neuropathy in Mice with a Distal Infraorbital Nerve Chronic Constriction Injury. International journal

    Takahiro Kochi, Yoki Nakamura, Simeng Ma, Kazue Hisaoka-Nakashima, Dengli Wang, Keyue Liu, Hidenori Wake, Masahiro Nishibori, Masahiro Irifune, Norimitsu Morioka

    Molecules (Basel, Switzerland)   26 ( 7 )   2021.4

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    DOI: 10.3390/molecules26072035

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  • Perineural high-mobility group box 1 induces mechanical hypersensitivity through activation of spinal microglia: Involvement of glutamate-NMDA receptor dependent mechanism in spinal dorsal horn. International journal

    Yoki Nakamura, Ayako Fukuta, Keita Miyashita, Fang Fang Zhang, Dengli Wang, Keyue Liu, Hidenori Wake, Kazue Hisaoka-Nakashima, Masahiro Nishibori, Norimitsu Morioka

    Biochemical pharmacology   186   114496 - 114496   2021.4

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    DOI: 10.1016/j.bcp.2021.114496

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  • Histidine-Rich Glycoprotein Stimulates Human Neutrophil Phagocytosis and Prolongs Survival through CLEC1A. International journal

    Yohei Takahashi, Hidenori Wake, Masakiyo Sakaguchi, Yukinori Yoshii, Kiyoshi Teshigawara, Dengli Wang, Masahiro Nishibori

    Journal of immunology (Baltimore, Md. : 1950)   206 ( 4 )   737 - 750   2021.2

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    DOI: 10.4049/jimmunol.2000817

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  • Anti-high mobility group box-1 (HMGB1) antibody therapy for spinal cord ischemia-reperfusion injury in rabbits

    Genya Muraoka, Liu Keyue, Qiao Handong, Ousaka Daiki, Wang Dengli, Fujii Yasuhiro, Kasahara Shingo, Nishibori Masahiro

    Proceedings for Annual Meeting of The Japanese Pharmacological Society   94   3-Y-F2-1   2021

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    Introduction

    Spinal cord ischemia and reperfusion (I/R) injury is one of the most devastating complications after thoracic and thoracoabdominal aortic aneurysm surgery. Several studies showed that levels of HMGB1 in serum were increased in patients who suffered from spinal cord I/R injury. These data strongly suggest that HMGB1 may play a crucial role in spinal cord I/R injury.

    Materials and Methods

    Male New Zealand white rabbits were used for the experiments. The abdominal aorta at the level of the left renal artery was exposed, and, after heparinization, occluded for 11 minutes. The rabbits were intravenously administered an anti-HMGB1 mAb (#10-22, 2mg/kg) or class-matched control IgG (anti-keyhole limpet hemocyanin mAb) twice immediately and 6h after reperfusion. The neurological findings were assessed at 6, 24 and 48 hours after reperfusion. At 48hr after reperfusion, the rabbits were sacrificed to obtain the specimen of spinal cord and blood samples.

    Results

    Administration of anti-HMGB1 mAb ameliorated the intensity of spinal cord infarction and preserved the number of motor neuron cells, in association with decreased activated microglia and astrocyte. Consequently, anti-HMGB1 mAb significantly improved the neurological outcomes after spinal I/R injury in rabbits.  These results strongly indicate that HMGB1 plays a critical role in the development of spinal cord I/R induced secondary injury through the amplification of inflammatory response.

    Conclusion

    Intravenous injection of neutralizing anti-HMGB1 mAb has potential as a novel therapeutic strategy for spinal cord I/R injury.

    DOI: 10.1254/jpssuppl.94.0_3-y-f2-1

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  • High Mobility Group Box-1 and Blood-Brain Barrier Disruption. International journal

    Masahiro Nishibori, Dengli Wang, Daiki Ousaka, Hidenori Wake

    Cells   9 ( 12 )   2020.12

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    DOI: 10.3390/cells9122650

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  • An Evaluation of the Activity of Histidine-Rich Glycoprotein on Differentiated Neutrophil-Like Cells from Human Cell Lines. International journal

    Yukinori Yoshii, Hidenori Wake, Yoshito Nishimura, Kiyoshi Teshigawara, Dengli Wang, Masahiro Nishibori

    The Journal of pharmacology and experimental therapeutics   375 ( 3 )   406 - 413   2020.12

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    DOI: 10.1124/jpet.120.000182

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  • Histidine-rich glycoprotein possesses antioxidant activity through self-oxidation and inhibition of hydroxyl radical production via chelating divalent metal ions in Fenton's reaction. International journal

    Hidenori Wake, Yohei Takahashi, Yukinori Yoshii, Shangze Gao, Shuji Mori, Dengli Wang, Kiyoshi Teshigawara, Masahiro Nishibori

    Free radical research   54 ( 8-9 )   649 - 661   2020.9

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    DOI: 10.1080/10715762.2020.1825703

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  • Histidine-Rich Glycoprotein Inhibits High-Mobility Group Box-1-Mediated Pathways in Vascular Endothelial Cells through CLEC-1A. International journal

    Shangze Gao, Hidenori Wake, Masakiyo Sakaguchi, Dengli Wang, Youhei Takahashi, Kiyoshi Teshigawara, Hui Zhong, Shuji Mori, Keyue Liu, Hideo Takahashi, Masahiro Nishibori

    iScience   23 ( 6 )   101180 - 101180   2020.6

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    DOI: 10.1016/j.isci.2020.101180

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  • Corticosterone Induces HMGB1 Release in Primary Cultured Rat Cortical Astrocytes: Involvement of Pannexin-1 and P2X7 Receptor-Dependent Mechanisms. International journal

    Kazue Hisaoka-Nakashima, Honami Azuma, Fumina Ishikawa, Yoki Nakamura, Dengli Wang, Keyue Liu, Hidenori Wake, Masahiro Nishibori, Yoshihiro Nakata, Norimitsu Morioka

    Cells   9 ( 5 )   2020.4

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    DOI: 10.3390/cells9051068

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  • HMGB1 Translocation in Neurons after Ischemic Insult: Subcellular Localization in Mitochondria and Peroxisomes. International journal

    Dengli Wang, Keyue Liu, Yusuke Fukuyasu, Kiyoshi Teshigawara, Li Fu, Hidenori Wake, Aiji Ohtsuka, Masahiro Nishibori

    Cells   9 ( 3 )   2020.3

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    DOI: 10.3390/cells9030643

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  • Histidine-rich glycoprotein ameliorates endothelial barrier dysfunction through regulation of NF-κB and MAPK signal pathway. International journal

    Shangze Gao, Hidenori Wake, Yuan Gao, Dengli Wang, Shuji Mori, Keyue Liu, Kiyoshi Teshigawara, Hideo Takahashi, Masahiro Nishibori

    British journal of pharmacology   176 ( 15 )   2808 - 2824   2019.8

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    DOI: 10.1111/bph.14711

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  • Histidine-rich glycoprotein augments natural killer cell function by modulating PD-1 expression via CLEC-1B. International journal

    Yoshito Nishimura, Hidenori Wake, Kiyoshi Teshigawara, Dengli Wang, Masakiyo Sakaguchi, Fumio Otsuka, Masahiro Nishibori

    Pharmacology research & perspectives   7 ( 3 )   e00481   2019.6

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    DOI: 10.1002/prp2.481

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  • The specific localization of advanced glycation end-products (AGEs) in rat pancreatic islets.

    Yuta Morioka, Kiyoshi Teshigawara, Yasuko Tomono, Dengli Wang, Yasuhisa Izushi, Hidenori Wake, Keyue Liu, Hideo Kohka Takahashi, Shuji Mori, Masahiro Nishibori

    Journal of pharmacological sciences   134 ( 4 )   218 - 224   2017.8

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    DOI: 10.1016/j.jphs.2017.07.005

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  • Anti-high mobility group box-1 (HMGB1) antibody inhibits hemorrhage-induced brain injury and improved neurological deficits in rats. International journal

    Dengli Wang, Keyue Liu, Hidenori Wake, Kiyoshi Teshigawara, Shuji Mori, Masahiro Nishibori

    Scientific reports   7   46243 - 46243   2017.4

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    DOI: 10.1038/srep46243

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  • Anti-HMGB1 therapy for intracerebral hemorrhage

    Dengli Wang, Katsuyaku Ryu, Hidenori Wake, Kiyoshi Teshigawara, Shuji Mori, Masahiro Nishibori

    JOURNAL OF PHARMACOLOGICAL SCIENCES   133 ( 3 )   S98 - S98   2017.3

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  • Anti-high mobility group box-1 (HMGB1) antibody attenuates delayed cerebral vasospasm and brain injury after subarachnoid hemorrhage in rats. International journal

    Jun Haruma, Kiyoshi Teshigawara, Tomohito Hishikawa, Dengli Wang, Keyue Liu, Hidenori Wake, Shuji Mori, Hideo Kohka Takahashi, Kenji Sugiu, Isao Date, Masahiro Nishibori

    Scientific reports   6   37755 - 37755   2016.11

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    DOI: 10.1038/srep37755

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  • Soluble form of the receptor for advanced glycation end-products attenuates inflammatory pathogenesis in a rat model of lipopolysaccharide-induced lung injury.

    Yasuhisa Izushi, Kiyoshi Teshigawara, Keyue Liu, Dengli Wang, Hidenori Wake, Katsuyoshi Takata, Tadashi Yoshino, Hideo Kohka Takahashi, Shuji Mori, Masahiro Nishibori

    Journal of pharmacological sciences   130 ( 4 )   226 - 34   2016.4

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    DOI: 10.1016/j.jphs.2016.02.005

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  • Anti-HMGB1 therapy for intracerebral hemorrhage

    Dengli Wang, Keyue Liu, Hidenori Wake, Kiyoshi Teshigawara, Shuji Mori, Masahiro Nishibori

    JOURNAL OF PHARMACOLOGICAL SCIENCES   130 ( 3 )   S88 - S88   2016.3

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  • Anti-HMGB1 therapy for intracerebral hemorrhage and vasospasm after subarachnoid hemorrhage

    Dengli Wang, Katsuyaku Ryu, Masahiro Nishibori

    JOURNAL OF PHARMACOLOGICAL SCIENCES   128 ( 3 )   S39 - S39   2015.7

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  • Contamination of Phenylobacterium in several human and murine cell cultures. International journal

    Tianqing Xiong, Dengli Wang, Baihong Tan, Wenhua Jiang, Gaoyue Dai, Hui Zhao, Shulei Li, Yanchao Li

    Wei sheng wu xue bao = Acta microbiologica Sinica   55 ( 2 )   176 - 86   2015.2

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    OBJECTIVE: To identify and characterize an unknown microorganism causing contamination in several mammalian cell cultures. METHODS: This bacterium was identified by 16S rRNA sequencing and studied by DAPI and DiOC6 (3) staining, Gram staining, acid-fast staining, and electron microscopy. The isolated bacterium was also used to infect host cells to observe antibiotic effectiveness and its relationship with host cells. RESULTS: The 16S rRNA sequence analysis shows that this rod-shaped microorganism belongs to the family Caulobacteraceae, class Alphaproteobacteria, and was most closely related to Phenylobacterium zucineum HLK1T strain. The bacterium collected in the "swimming" stage was Gram staining negative, but Gram staining positive in the "sessile" stage. Under the electron microscope both flagellated and non-flagellated types were found. So far, no antibiotics were effective to inhibit this microorganism. The contamination with this bacterium frequently led to failed resuscitation of thawed cells. We found that the cells resuscitated with the used culture supernatants were increased in number by 3-4 folds as compared to those resuscitated with freshly prepared media. CONCLUSION: Phenylobacterium may have a dimorphic life cycle including a swimming stage and a sessile stalked stage.

    PubMed

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MISC

  • Role of HMGB1 derived from macrophages and enteric glial cells in the butyrate-induced colonic hypersensitivity

    佐々木花菜, SHIN Eunkyung, 野中結, 坪田真帆, WANG Dengli, 西堀正洋, 川畑篤史

    日本薬学会年会要旨集(Web)   142nd   2022

  • Anti-platelet agents prevent oxaliplation-induced peripheral neuropathy (OIPN): involvement of platelet-derived HMGB1 in OIPN

    川畑篤史, 岸本彩野, 堂本莉紗, 松永浩明, 松本亜紗菜, 坪田真帆, 関口富美子, WANG Dengli, 西堀正洋

    Pain Research   37 ( 4 )   2022

  • 活性化プロテインCは神経障害性疼痛を抑制する:Proteinase-activated receptor-1(PAR1)の関与について

    圓尾賢悟, 池田裕哉, 坪田真帆, 王登莉, 西堀正洋, 南達郎, 伊藤彰敏, 川畑篤史

    生体機能と創薬シンポジウム要旨集   2022   2022

  • Oxaliplatin誘起末梢神経障害には血小板由来HMGB1が関与する

    岸本彩野, 堂本莉紗, 松永浩明, 松本亜紗菜, 坪田真帆, 関口富美子, 王登莉, 西堀正洋, 川畑篤史

    日本薬理学雑誌   157 ( Supplement )   2022

  • Distinct mechanisms for release of HMGB1 from macrophages involved in the peripheral neuropathy induced by chemotherapeutic agents, bortezomib and vincristine

    青木葉優衣, 谷津健太, 池田裕哉, 関口富美子, 坪田真帆, WANG Dengli, 西堀正洋, 川畑篤史

    日本薬学会年会要旨集(Web)   142nd   2022

  • TLR2はAGE2刺激による細胞増殖を抑制する

    豊村 隆男, 渡邊 政博, 和氣 秀徳, 逢坂 大樹, 王 登莉, 高橋 英夫, 西堀 正洋, 森 秀治

    日本薬学会年会要旨集   141年会   28P02 - 189   2021.3

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  • Treatment of intracerebral hemorrhage with humanized a-HMGB1 mAb in non-human primate brain

    王登莉, 喬寒棟, 逢坂大樹, 西堀正洋

    日本薬理学雑誌   156 ( Supplement )   2021

  • ウサギを用いた脊髄虚血再灌流障害モデルに対する抗HMGB1抗体の有用性の検討

    村岡玄哉, 劉克約, 喬寒棟, 逢坂大樹, 王登莉, 藤井泰宏, 笠原真悟, 西堀正洋

    日本胸部外科学会定期学術集会(Web)   74th   2021

  • グリコールアルデヒド由来AGEsによる細胞増殖機構

    豊村隆男, 渡邊政博, 和氣秀徳, 西中崇, 逢坂大樹, 王登莉, 高橋英夫, 西堀正洋, 森秀治

    日本生化学会大会(Web)   94th   2021

  • 終末糖化産物AGE2による細胞増殖効果とTLR2による制御

    豊村隆男, 渡邊政博, 和氣秀徳, 逢坂大樹, 王登莉, 高橋英夫, 西堀正洋, 森秀治

    日本生化学会大会(Web)   93rd   2020

  • TLR2によるAGE2依存的な細胞増殖制御

    豊村隆男, 渡邊政博, 和氣秀徳, 逢坂大樹, 王登莉, 高橋英夫, 西堀正洋, 森秀治

    日本分子生物学会年会プログラム・要旨集(Web)   43rd   2020

  • The effect of anti-HMGB1 antibody on collagenase-induced intracerebral hemorrhage in rats

    Katsuyaku Ryu, Dengli Wang, Hidenori Wake, Kiyoshi Teshigawara, Hideo Takahashi, Shuji Mori, Masahiro Nishibori

    JOURNAL OF PHARMACOLOGICAL SCIENCES   124   189P - 189P   2014

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Presentations

  • 抗HMGB1抗体による脳内出血の治療:霊長類マーモセットを用いた検討

    王登莉

    第36回 創薬・薬理フォーラム岡山  2021.12.25  広島大学薬効解析科学教室

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    Event date: 2021.12.25

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  • The therapeutic effects of humanized anti-HMGB1 mAb on intracerebral hemorrhage-induced brain injury in marmoset

    Dengli Wang

    2021.7.31 

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    Event date: 2021.7.28 - 2021.7.31

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  • The therapeutic effects of anti-HMGB1 mAb on subdural hematoma-induced brain injury in rats

    Dengli Wang

    2020.7.29 

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    Event date: 2020.7.28 - 2020.8.1

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  • Effects of anti-HMGB1 mAb in various models of brain injury Invited

    Dengli Wang

    Soochow University Forum for Overseas High-level Talents  2019.12.27 

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    Event date: 2019.12.26 - 2019.12.28

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  • Anti-HMGB1 therapy for intracerebral and subdural hemorrhage-induced brain injury in rats

    Dengli Wang

    9th International DAMPs and Alarmins Symposium  2019.11.7 

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    Event date: 2019.11.6 - 2019.11.8

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  • Anti-HMGB1 mAb ameliorates intracerebral hemorrhage-induced brain injury in rats

    Dengli Wang

    2018.7.27 

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    Event date: 2018.7.26 - 2018.7.29

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  • Anti-HMGB1 mAb therapy for intracerebral hemorrhage-induced brain injury in rats

    Dengli Wang

    18th World Congress of Basic and Clinical Pharmacology  2018.7.3 

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    Event date: 2018.7.1 - 2018.7.6

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  • Treatment of intracerebral hemorrhage with humanized a-HMGB1 mAb in non-human primate brain

    Dengli Wang

    2021.6.26 

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  • HMGB1 Translocation in Neurons after Ischemic Insult: Subcellular Localization in Mitochondria and Peroxisomes

    Dengli Wang

    2020.6.20 

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  • Anti-HMGB1 mAb therapy for intracerebral and subdural hemorrhage in rats

    Dengli Wang

    2020.3 

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  • Anti-HMGB1 therapy for intracerebral and subdural hemorrhage-induced brain injury in rats

    Dengli Wang

    2019.7 

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  • Anti-HMGB1 mAb ameliorates intracerebral hemorrhage-induced brain injury in rats

    Dengli Wang

    2018.7 

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Awards

  • 優秀演題賞

    2016.6   第37回日本炎症・再生医学会  

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  • 国際交流奨励賞

    2015.3   公益信託岡山ロータリークラブ国際交流振興基金  

    王登莉

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Research Projects

  • Development of a novel therapeutic drug targeting ribonucleoprotein for glioblastoma model

    Grant number:24K18540  2024.04 - 2027.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    王 登莉

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    Grant amount:\4680000 ( Direct expense: \3600000 、 Indirect expense:\1080000 )

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  • Validation and drug development for anti-cancer therapy targeting hemolysis-hemopexin related axis

    Grant number:22K07253  2022.04 - 2025.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    逢坂 大樹, 王 登莉, 細野 祥之

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    Grant amount:\4160000 ( Direct expense: \3200000 、 Indirect expense:\960000 )

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  • HMGB1-HRGバランスに着目した川崎病新規治療薬の開発

    Grant number:21K07822  2021.04 - 2024.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    馬場 健児, 平井 健太, 西堀 正洋, 逢坂 大樹, 王 登莉

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    Grant amount:\4160000 ( Direct expense: \3200000 、 Indirect expense:\960000 )

    2021年度は、川崎病急性期患者における血中HMGB1、HRG濃度の測定において大きな成果が得られた。予定していた人数で川崎病急性期患者における治療前と初回治療後の血漿検体採取が終了し、コントロールとして健常者の検体と血中HMGB1、HRG濃度の比較を行ったところ、川崎病患者では健常者に比べて血中HMGB1が有意に高値、血中HRGが有意に低値であった。さらに川崎病患者を初回治療反応群、不応群に分け、治療前後の血中HMGB1、HRG濃度の変化についても詳細な解析を行い、論文投稿の準備を進めている。
    また川崎病モデルマウスの実験に関しては、Lactobacillus cell wall extract(LCWE)を作成し、マウスに腹腔内投与することで、川崎病様の冠動脈炎が惹起されることを確認した。しかし個体によって冠動脈炎の程度にばらつきが大きかったため、同様に川崎病冠動脈炎を惹起するCandida albicans water soluble fraction(CAWS)を用いるモデルについても検討を行った。CAWSを作成してマウスに腹腔内投与したところ、LCWEよりも安定してモデル作成ができることが明らかとなったため、以後の検討ではCAWSを腹腔内投与するモデルを使用することとした。

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  • Verification of preventative effects of monoclonal HMGB1 antibody for spinal cord injury after aortic operation

    Grant number:21K08823  2021.04 - 2024.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    村岡 玄哉, 大澤 晋, 藤井 泰宏, 王 登莉, 西堀 正洋, 逢坂 大樹, 笠原 真悟

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    Grant amount:\4030000 ( Direct expense: \3100000 、 Indirect expense:\930000 )

    胸部下行・胸腹部の大動脈瘤手術は大動脈ステントグラフトの発達に伴いハイリスク患者
    でも積極治療されるようになり、急激に患者数が増加している。本邦での最新の胸部・胸腹部大動脈手術数は35,427例(2015年1月~2016年2月)である。一方、これらの疾患群の死亡率は平均7.3%と高く、生命予後に大きく関わる非常に重大な合併症として、脊髄虚血による対麻痺が挙げられる。対麻痺は術式にもよるが、3.4~10.4% の確率で発生しており、かなりの数の患者が対麻痺を発症している。(日心外科誌48巻1号: 18-24, 2019)。この発生率は、既存の脊髄保護法(Naroxone投与、冷却、脊髄ドレナージ、Adamkiewics動脈再建、ステロイド等)を適宜行った上での数値であり、新たな対策・治療法開発は喫緊の課題である。我々はこれまで、岡山大学薬理学の西堀らが独自に開発した抗HMGB1(high mobility group box 1)抗体を用い、脳虚血、くも膜下出血、硬膜下出血、脳外傷といった中枢神経疾患動物モデルでその脳障害予防効果を証明してきた。そこで、心臓血管外科手術における脊髄保護にも有用ではないかと考え、ウサギの脊髄虚血モデル作成のPreliminary Study を施行後、本研究を計画した。本研究の目的は、NSC 34 Cell を分化させた、Motor Neuron Like Cellとうさぎ脊髄虚血モデルを用いて、HMGB1抗体のMotor Neuron に対する細胞死抑制効果、酸化ストレス抑制効果を実証し、臨床応用へ繋げる事である。本年度は、計画している実験のうち、ウサギを用いた実験を行い、細胞を使用する実験は来年以降に行うこととした。ウサギの脊髄虚血モデルを用いた抗HMGB-1抗体の脊髄麻痺予防効果実証実験R3年度予定分を施行した。

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  • Application of anti-HMGB1 m Ab in intracerebral hemorrhage-induced brain injury in common marmoset and elucidation of HMGB1 translocation mechanism

    Grant number:20K17930  2020.04 - 2024.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    王 登莉

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    Grant amount:\4160000 ( Direct expense: \3200000 、 Indirect expense:\960000 )

    令和2年度の研究計画では霊長類マーモセット脳出血モテルにおけるヒト化抗 HMGB1 抗体の効果の確認を目的とした。 マーモセットの右基底核にコラケナーゼIVを定位的に注入することで脳出血モデルを作成した。脳出血モデル作成後10分間にヒト化抗 HMGB1抗体を尾静脈から投与した。対照動物には、ヒトIgGを投与した。2時間、6時間、1日、2日、3日、6日、12日後に採血し、体重を測定した。神経学的評価は、経時的にgrip strengthテストを実施した。脳損傷に対する抗HMGB1 の効果を測定するために、脳出血後6、12 日後の CT 像を撮像し脳組織損傷範囲を評価した。12日後に脳を取り出しHE染色や免疫染色をした。その結果、抗HMGB1抗体の投与によって、血漿中HMGB1と酸化ストレスマーカーである4-HNEの有意に抑制を示した。出血後から12日間、対照動物の体重がずっと減少することが明瞭であったが、抗HMGB1抗体の投与によって3日間から回復し6日間で出血前の体重に戻った。grip strengthテストによる評価で、運動麻痺神経症状も、抗HMGB1抗体で高い改善効果を示した。また、脳出血12日C T像から見ると、抗HMGB1抗体の投与によって脳組織損傷範囲は減少した。

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  • 組織障害性HMGB1に着眼した肺虚血再灌流障害に対する新規戦略の確立

    Grant number:20K09176  2020.04 - 2023.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    大谷 真二, 山根 正修, 豊岡 伸一, 杉本 誠一郎, 王 登莉, 西堀 正洋, 岡崎 幹生, 三好 健太郎, 阪口 政清

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    Grant amount:\4290000 ( Direct expense: \3300000 、 Indirect expense:\990000 )

    ①マウス肺門クランプモデルにおけるHMGB1の動態:HMGB1は通常核内に限局しているタンパクである。マウス左肺門クランプモデルにおいて、再還流後2時間までのHMGB1の血中濃度を測定したところ、HMGB1が時系列に沿って上昇することが確認された。また組織の免疫染色において、虚血再還流障害を加えた群では、HMGB1が核内よりむしろ細胞質で強く染色され、細胞障害性の刺激により核内から細胞質へ移動している様子が確認された。この現象はHMGB1抗体を投与することで抑制されたことから細胞障害によりHMGB1には自己分泌経路が出現し抗体投与によってその経路を停止させることができるのではないか、と考えられた。
    ②抗体投与による虚血再還流障害の抑制:HMGB1抗体を投与する事による虚血再還流障害の抑制効果を調べた。肺機能、組織障害の改善を生理学的、組織学的に確認することができた。
    ③抗体投与による抗炎症効果:HMGB1抗体を投与するとサイトカインの産生が低下することが確認された。HMGB1はRAGEやTLRといったレセプターのリガンドであり、MAPKの経路を介しサイトカイン産生を行っているが、HMGB1抗体によりMAPKの経路が抑制されることが示された。
    ④抗体投与によるアポトーシスの抑制:肺組織の細胞死を定量するため組織でのアポトーシスを検索した。虚血性再還流障害によるアポトーシスが抗体投与により抑制されていることが確認された。

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  • 敗血症関連DAMPs拮抗因子HRGの血管保護作用機序の解明

    Grant number:20K07290  2020.04 - 2023.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    和氣 秀徳, 勅使川原 匡, 王 登莉

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    Grant amount:\4420000 ( Direct expense: \3400000 、 Indirect expense:\1020000 )

    HRGのフェロトーシス細胞死への関与を明らかにするために、血管内皮細胞株EA.hy926細胞へ2価鉄もしくは3価鉄で刺激を行い、鉄による細胞障害性をMTSアッセイを用いて評価した。2価の鉄は鉄を添加していない群や3価の鉄を添加した群と比較して、著しい細胞活動の低下を示し、HRGはこの低下をほぼ完全に抑制した。また細胞非透過性の核染色剤SytoxOrangeを用いて細胞膜完全性の評価を行ったところ、2価の鉄は鉄を添加していない群や3価の鉄を添加した群と比較して、細胞膜が障害されており、HRGはこの細胞膜障害を抑制した。さらに、細胞膜脂質過酸化状態を過酸化脂質蛍光染色剤で評価したところ、2価鉄刺激により細胞膜の酸化が引き起こされ、HRGはこれを抑制することを明らかにした。つまり、HRGは2価鉄による細胞膜酸化障害を抑制することで、細胞を保護する活性を有することが明らかとなった。
    HRGのパイロトーシス経路への関与に関しては、以前からパイロトーシスを誘導することで知られているLPSにより、パイロトーシスへの関与が疑われるHMGB1の血管内皮細胞核内から細胞外へのトランスロケーションを誘導することを明らかにしていたが、HRGはCLEC1Aを介して、このHMGB1トランスロケーションを阻害することを新たに示した。
    HRGの血管内皮細胞表面上のグリコカリックスの状態に対する影響に関しては、マウスの血管内皮細胞表面グリコカリックスをを蛍光標識レクチンで染色し、インビボイメージングにより、その状態を評価した。LPSのi.v.投与により、蛍光標識レクチンで染色されない血管が増加し、HRG KOマウスではその割合がさらに増加することから、血中のHRGはLPSによるグリコカリックスの剥離を抑制する効果を有することが示唆された。

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  • Analysis dynamics of HMGB1 as a biosensor molecule and its multiple functions

    Grant number:19H03408  2019.04 - 2022.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Nishibori Masahiro

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    Grant amount:\17550000 ( Direct expense: \13500000 、 Indirect expense:\4050000 )

    Dynamics of a representative DAMP, HMGB1, was examined using vascular endothelial cells (EA.hy926). Histamine concentration-dependently induced the translocation and release of HMGB1 from vascular endothelial cells by the stimulation of H1-receptor subtype, which was mimicked by selective H1- receptor agonist, 2-pyridyl-ethylamine. Mast cell stimulator, compound 48/80, induced an anaphylactic hypotensive shock in rats, associated with the elevation of plasma HMGB1. The treatment with anti-HMGB1 mAb (#10-22) significantly facilitated the recovery from hypotensive shock.
    LPS and TNF-α induced a similar HMGB1 release from vascular endothelial cells, associated with the secretion of IL-6 and IL-8. All these responses were inhibited by anti-HMGB1 mAb (#10-22). Taken together, it was concluded that HMGB1 in vascular endothelial cells may respond to many stimulants.

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  • Roles of histidine-rich glycoprotein in prevention of hypertensive disorders of pregnancy and in physiological placental development.

    Grant number:19K07401  2019.04 - 2022.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Teshigawara Kiyoshi

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    Grant amount:\4290000 ( Direct expense: \3300000 、 Indirect expense:\990000 )

    Histidine-rich glycoprotein (HRG) is an anti-inflammatory factor that controls the progression of systemic inflammatory pathology. Recently, it was reported that an excess reduction of plasma HRG level in human pregnant was correlated with the hypertensive disorders of pregnancy (HDP) seriousness. In this study, we examined the involvement of plasma HRG on the gestational period using C57BL/6 mice and HRG gene-deficient (HRG KO) mice. In the healthy gestational mice, plasma HRG level was decreased and hysterectomy restored the reduced-plasma HRG up to the pre-gestational level. Moreover, HRG KO mice showed hypertension by the gestation, whereas rise in blood pressure did not observed in the healthy gestational mice. These results suggest that plasma HRG may have a physiological function in gestational period. Gestational HRG KO mice may be a HDP-like pathological model.

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  • 敗血症治療のためのHRG血液製剤の創出

    Grant number:19im0210109  2017.10 - 2020.03

    日本医療研究開発機構 (AMED)  医療分野研究成果展開事業  産学連携医療イノベーション創出プログラム 基本スキーム (ACT-M)

    西堀正洋, 和氣秀徳, 阪口政清, 宝田剛志, 勅使川原匡, 王登莉, 森松博史, 吉田道弘, 伊藤浩和, 上園昭人, 村上弘次, 前野英毅, 須加智也, 小林不二夫, 福永裕樹

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Social Activities

  • 2023 ONECUS Program Autumn Seminar

    Role(s):Presenter

    2022.11.9

  • Okayama University-North East China Universities platform, Graduate Student Exchange Program.

    Role(s):Presenter

    2022.11

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  • 中国・浙江大学医学部生 岡山大学夏期フロクラム

    Role(s):Lecturer

    2018.7 - 2019.7

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    Type:Other

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