Updated on 2022/04/12

写真a

 
ITOH Michiko
 
Organization
Research Institute of Environmental Medicine Division of Stress Recognition and Response Designated associate professor
Title
Designated associate professor

Degree 1

  1. 博士(医学) ( 2009.3   東京医科歯科大学 ) 

Research Interests 5

  1. non-alcoholic steatohepatitis

  2. obesity

  3. chronic inflammation

  4. metabolic syndrome

  5. macrophage

Research Areas 3

  1. Life Science / Embryonic medicine and pediatrics

  2. Life Science / Experimental pathology

  3. Life Science / Metabolism and endocrinology

Research History 3

  1. 名古屋大学環境医学研究所メタボ栄養科学寄附研究部門   特任准教授

    2021.4

  2. 神奈川県立産業技術総合研究所   「貼るだけ人工膵臓」プロジェクト   サブリーダー

    2019.4

  3. Tokyo Medical and Dental University   Graduate School of Medical and Dental Sciences   Designated associate professor

    2018.4 - 2019.3

Professional Memberships 10

  1. JAPAN SOCIETY FOR THE STUDY OF OBESITY

  2. THE JAPAN DIABETES SOCIETY

  3. 日本糖尿病・肥満動物学会

  4. 日本生理学会

  5. 日本生化学会

  6. THE JAPANESE SOCIETY OF INFLAMMATION AND REGENERATION

  7. JAPAN PEDIATRIC SOCIETY

  8. THE JAPANESE SOCIETY FOR PEDIATRIC ENDOCRINOLOGY

  9. The Japan Endocrine Society

  10. 日本Cell death学会

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Awards 1

  1. 第41回日本肥満学会学術奨励賞

    2021   日本肥満学会  

 

Papers 7

  1. Boronic Acid Ligands Can Target Multiple Subpopulations of Pancreatic Cancer Stem Cells via pH-Dependent Glycan-Terminal Sialic Acid Recognition

    Miyazaki Takuya, Khan Thahomina, Tachihara Yoshihiro, Itoh Michiko, Miyazawa Taiki, Suganami Takayoshi, Miyahara Yuji, Cabral Horacio, Matsumoto Akira

    ACS APPLIED BIO MATERIALS   Vol. 4 ( 9 ) page: 6647 - 6651   2021.9

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    Language:Japanese   Publisher:ACS Applied Bio Materials  

    Eradication of cancer stem cells (CSCs) is an ultimate goal in cancer chemotherapy. Although a ligand-assisted targeting approach seems rational, the existence of subpopulations of CSCs and their discrimination from those present on healthy sites makes it a severe challenge. Some boronic acid (BA) derivatives are known for the ability to bind with glycan-terminal sialic acid (SA), in a manner dependent on the acidification found in hypoxic tumoral microenvironment. Taking advantage of this feature, here we show that the BA-ligand fluorescence conjugate can effectively target multiple CSC subpopulations in parallel, which otherwise must be independently aimed when using antibody-ligands.

    DOI: 10.1021/acsabm.1c00383

    Web of Science

    Scopus

  2. The sodium-glucose cotransporter-2 inhibitor Tofogliflozin prevents the progression of nonalcoholic steatohepatitis-associated liver tumors in a novel murine model

    Yoshioka Naoki, Tanaka Miyako, Ochi Kozue, Watanabe Akiko, Ono Kenji, Sawada Makoto, Ogi Tomoo, Itoh Michiko, Ito Ayaka, Shiraki Yukihiro, Enomoto Atsushi, Ishigami Masatoshi, Fujishiro Mitsuhiro, Ogawa Yoshihiro, Suganami Takayoshi

    BIOMEDICINE & PHARMACOTHERAPY   Vol. 140   page: 111738   2021.8

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    Language:Japanese   Publisher:Biomedicine and Pharmacotherapy  

    Background: Diabetes and obesity contribute to the pathogenesis of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). However, how diabetes and obesity accelerate liver tumorigenesis remains to be fully understood. Moreover, to verify the therapeutic potential of anti-diabetic drugs, there exists a strong need for appropriate animal models that recapitulate human pathophysiology of NASH and HCC. Methods: We established a novel murine model of NASH-associated liver tumors using genetically obese melanocortin 4 receptor-deficient mice fed on Western diet in combination with a chemical procarcinogen, and verified the validity of our model in evaluating drug efficacy. Findings: Our model developed multiple liver tumors together with obesity, diabetes, and NASH within a relatively short period (approximately 3 months). In this model, sodium glucose cotransporter 2 inhibitor Tofogliflozin prevented the development of NASH-like liver phenotypes and the progression of liver tumors. Tofogliflozin attenuated p21 expression of hepatocytes in non-tumorous lesions in the liver. Interpretation: Tofogliflozin treatment attenuates cellular senescence of hepatocytes under obese and diabetic conditions. This study provides a unique animal model of NASH-associated liver tumors, which is applicable for assessing drug efficacy to prevent or treat NASH-associated HCC.

    DOI: 10.1016/j.biopha.2021.111738

    Web of Science

    Scopus

    PubMed

  3. NASHにおけるクッパー細胞鉄代謝の病態生理学的意義

    金森 耀平, 田中 都, 伊藤 美智子, 越智 梢, 伊藤 綾香, 日高 勲, 坂井田 功, 小川 佳宏, 菅波 孝祥

    日本内分泌学会雑誌   Vol. 97 ( 1 ) page: 255 - 255   2021.4

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    Language:Japanese   Publisher:(一社)日本内分泌学会  

  4. Iron-rich Kupffer cells exhibit phenotypic changes during the development of liver fibrosis in NASH. Reviewed International journal

    Yohei Kanamori, Miyako Tanaka, Michiko Itoh, Kozue Ochi, Ayaka Ito, Isao Hidaka, Isao Sakaida, Yoshihiro Ogawa, Takayoshi Suganami

    iScience   Vol. 24 ( 2 ) page: 102032 - 102032   2021.2

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    Although recent evidence suggests the involvement of iron accumulation in the pathogenesis of nonalcoholic steatohepatitis (NASH), the underlying mechanisms remain poorly understood. Previously, we reported a unique histological structure termed "crown-like structure (CLS)," where liver-resident macrophages (Kupffer cells) surround dead hepatocytes, scavenge their debris, and induce inflammation and fibrosis in NASH. In this study, using magnetic column separation, we show that iron-rich Kupffer cells exhibit proinflammatory and profibrotic phenotypic changes during the development of NASH, at least partly, through activation of MiT/TFE transcription factors. Activation of MiT/TFE transcription factors is observed in Kupffer cells forming CLSs in murine and human NASH. Iron chelation effectively attenuates liver fibrosis in a murine NASH model. This study provides insight into the pathophysiologic role of iron in NASH. Our data also shed light on a unique macrophage subset rich in iron that contributes to CLS formation and serves as a driver of liver fibrosis.

    DOI: 10.1016/j.isci.2020.102032

    Web of Science

    Scopus

    PubMed

  5. 異所性脂肪と肝疾患

    伊藤 美智子

    外科と代謝・栄養   Vol. 55 ( 3 ) page: 133 - 136   2021

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    Language:Japanese   Publisher:日本外科代謝栄養学会  

     肥満人口の増大に伴って, 過栄養による肝異所性脂肪蓄積を基盤とする非アルコール性脂肪性肝疾患 (non‐alcoholic fatty liver disease:以下NAFLD) が世界的に増加している. NAFLDの中で単純性脂肪肝は一般的に予後良好であるが, 炎症・線維化を特徴とする非アルコール性脂肪性肝炎 (non‐alcoholic steato‐hepatitis: 以下NASH) は肝硬変・肝細胞癌に進展する重症型である. 単純性脂肪肝では主に細胞保護的な中性脂肪が蓄積するのに対し, NASHではコレステロールをはじめとする細胞障害性のある脂質の増加が指摘されている. これらの脂質がもたらす「脂肪毒性」は肝細胞死を誘導するだけでなく, 間質細胞における炎症・線維化促進経路を活性化することでNASHの病態形成に寄与すると考えられる. 特にマクロファージは死細胞の貪食にあたることから, 死細胞に由来する脂質がマクロファージの疾患特異的活性化を制御する可能性がある. 異所性脂肪蓄積の分子メカニズムと脂肪毒性の本態を理解することで, NASH発症機構の解明と新規治療標的の探索に繋がると考えられる.

    DOI: 10.11638/jssmn.55.3_133

  6. Role of chronic inflammation in the pathogenesis of nonalcoholic steatohepatitis: lessons from a unique mouse model using melanocortin receptor-deficient mice

    Itoh Michiko, Suganami Takayoshi, Ogawa Yoshihiro

    Endocrine Journal   Vol. 68 ( 7 ) page: 743 - 749   2021

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    Language:English   Publisher:一般社団法人 日本内分泌学会  

    <p>Nonalcoholic fatty liver disease (NAFLD) is a clinical spectrum that encompasses simple steatosis to nonalcoholic steatohepatitis (NASH), the latter of which is characterized by chronic inflammation and fibrosis. NASH is now becoming the leading cause of cirrhosis and hepatocellular carcinoma worldwide. The pathophysiology of NASH is multifactorial and, therefore, not yet completely understood, although it is pointed out that hepatocyte death and subsequent inflammation play a central roles in disease pathogenesis. Since stromal cells dramatically change their cellular components and activation status as liver fibrosis develops, it is important to reveal the subset responsible for the disease development in each etiology. Macrophages foam crown-like structures (CLS), in which CD11c-positive macrophages surround dead hepatocytes induced by lipotoxic injury in mouse and human NASH. Hepatic CLS-constituting macrophages exhibit gene expression profiles distinct from other scattered macrophages in the liver, suggesting NASH-specific macrophages represent a subset that drives metabolic stress-induced liver fibrosis. Moreover, cancer-associated pathways are upregulated in activated fibroblasts from the liver of a mouse NASH model, suggesting that fibroblasts provide the microenvironment that promotes tumor progression. A better understanding of the upstream signals and regulatory mechanisms that drive the generation of NASH-specific macrophage and fibroblast subsets is crucial for the development of novel diagnostic and therapeutic strategies.</p>

    DOI: 10.1507/endocrj.EJ21-0002

    Scopus

    PubMed

  7. Role of chronic inflammation in the pathogenesis of nonalcoholic steatohepatitis: lessons from a unique mouse model using melanocortin receptor-deficient mice

    Itoh Michiko, Suganami Takayoshi, Ogawa Yoshihiro

    ENDOCRINE JOURNAL   Vol. 68 ( 7 ) page: 743 - 749   2021

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    Language:Japanese  

    Web of Science

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Presentations 5

  1. Role of cholesterol metabolism in macrophages in the pathogenesis of non-alcoholic steatohepatitis Invited

    Michiko Itoh, Takayoshi Suganami

    2021.3.30 

  2. 新規NASHマウスモデルの開発と病態形成機構の解明 Invited

    伊藤美智子, 菅波孝祥, 小川佳宏

    第41回日本肥満学会学術集会  2021.3.21 

  3. NASH発症過程における死細胞貪食障害の病態生理的意義

    伊藤美智子, 金井紗綾香, 金森耀平, 田中都, 松元亮, 宮原裕二, 小川佳宏, 菅波孝祥

    第41回日本肥満学会学術集会  2021.3.21 

  4. NASH発症における死細胞貪食・処理の病態生理的意義 Invited

    伊藤美智子, 田中都, 小川佳宏, 菅波孝祥

    日本Cell Death学会第29回学術集会  2021.7.26 

  5. NASHマウスモデルの確立を通じた病態解析・治療戦略開発への挑戦 Invited

    伊藤美智子, 小川佳宏, 菅波孝祥

    第64回日本糖尿病学会学術集会  2021.5.20 

KAKENHI (Grants-in-Aid for Scientific Research) 3

  1. 細胞死を起点とする非アルコール性脂肪性肝炎の発症機構解明と治療戦略開発

    2020 - 2021

    公益財団法人MSD生命科学財団  研究助成2019 -生活習慣病領域-【若手研究者】 

  2. Cell death-induced inflammation and the development of NASH and hepatocellular carcinoma

    Grant number:19K07475  2019.4 - 2022.3

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

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    Authorship:Principal investigator 

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

  3. 疾患特異的線維芽細胞に基づくNASH・肝癌予防医療に関する研究

    2019

    公益財団法人テルモ生命科学振興財団  2019年度 III.研究助成金 

Industrial property rights 1

  1. 非アルコール性脂肪肝炎モデル動物の製造方法

    菅波孝祥, 伊藤美智子, 小川佳宏

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    Application no:特願2015-122913