Molecular mechanism of cell death-induced tissue remodeling in metabolic syndrome
Project/Area Number |
20H03447
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 49010:Pathological biochemistry-related
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Research Institution | Nagoya University |
Principal Investigator |
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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Keywords | 慢性炎症 / メタボリックシンドローム / マクロファージ / 肥満 / NASH / 肝がん / 非アルコール性脂肪肝炎 |
Outline of Research at the Start |
近年、過栄養に伴う代謝ストレスが慢性炎症を誘導し、生活習慣病の病態基盤となることが注目されている。研究代表者は、代謝ストレスによる細胞死が自然免疫応答を惹起して、メタボリックシンドロームにおける慢性炎症をもたらすことを見出した。本研究では、どのような細胞死が、どのようにして疾患・臓器特異的に炎症慢性化をもたらすかを解明し、新たな病態メカニズムの解明を目指す。
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Outline of Final Research Achievements |
To elucidate the molecular mechanisms of chronic inflammation associated with overnutrition, this study focused on the unique histological feature "crown-like structure (CLS)" observed in obesity and non-alcoholic steatohepatitis (NASH), and investigated the molecular mechanism of CLS formation and its pathophysiological significance. Specifically, we addressed (1) the application of the plant-derived flavonoid taxifolin to the treatment of NASH, (2) the functional significance of iron-rich macrophages in NASH, and (3) the mechanism of hepatic fibrosis induced by altered macrophage cholesterol metabolism.
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Academic Significance and Societal Importance of the Research Achievements |
現在、NASHの病態メカニズムは未だ不明の点が多く、厚労省に認可されたNASH治療薬も存在しない。本研究では、既に健康食品として世界中で使用されているタキシフォリンが抗メタボリックシンドローム効果に加えて、抗NASH効果も有することを初めて明らかにするとともに、CLSが薬効評価の点で有用であることを示した。また、鉄やコレステロールに着目してNASH病態メカニズムの一端を明らかにし、新たな治療戦略の創出につながると期待できる。
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Report
(4 results)
Research Products
(44 results)
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[Journal Article] Obesity accelerates hair thinning by stem cell-centric converging mechanisms2021
Author(s)
Morinaga H, Mohri Y, Grachtchouk M, Asakawa K, Matsumura H, Oshima M, Takayama N, Kato T, Nishimori Y, Sorimachi Y,?Takubo K, Suganami T, Iwama A, Iwakura Y, Dlugosz AA, Nishimura EK.
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Journal Title
Nature
Volume: 595
Issue: 7866
Pages: 266-271
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] The sodium-glucose cotransporter-2 inhibitor Tofogliflozin prevents the progression of nonalcoholic steatohepatitis-associated liver tumors in a novel murine model.2021
Author(s)
Yoshioka N, Tanaka M, Ochi K, Watanabe A, Ono K, Sawada M, Ogi T, Itoh M, Ito A, Shiraki Y, Enomoto A, Ishigami M, Fujishiro M, Ogawa Y, Suganami T.
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Journal Title
Biomed Pharmacother
Volume: 140
Pages: 111738-111738
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome2020
Author(s)
Oka Y, Hamada M, Nakazawa Y, ..., Tanaka M, Suganami T, Nakada S, Mitsutake N, Hara Y, Kato K, ..., Kaneko H, Matsumoto N, Matsuda F, Matsuo K, Takahashi Y, Mashimo T, Kojima S, Ogi T
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Journal Title
Science Advances
Volume: 6
Issue: 51
Pages: 7197-7197
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] C-type lectin Mincle mediates cell death-triggered inflammation in acute kidney injury.2020
Author(s)
Tanaka M, Saka-Tanaka M, Ochi K, Fujieda K, Sugiura Y, Miyamoto T, Kohda H, Ito A, Miyazawa T, Matsumoto A, Aoe S, Miyamoto Y, Tsuboi N, Maruyama S, Suematsu M, Yamasaki S, Ogawa Y, Suganami T.
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Journal Title
J Exp Med.
Volume: 217
Issue: 11
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Blocking sphingosine 1-phosphate receptor 2 accelerates hepatocellular carcinoma progression in a mouse model of NASH2020
Author(s)
Yoshida T, Tsuchiya A, Kumagai M, Takeuchi S, Nojiri S, Watanabe T, Ogawa M, Itoh M, Takamura M, Suganami T, Ogawa Y, Terai S.
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Journal Title
Biochem Biophys Res Commun
Volume: 530
Issue: 4
Pages: 665-672
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Hollow fiber-combined glucose-responsive gel technology as an in vivo electronics-free insulin delivery system.2020
Author(s)
Matsumoto A, Kuwata H, Kimura S, Matsumoto H, Ochi K, Moro-oka Y, Watanabe A, Yamada H, Ishii H, Miyazawa T, Chen S, Baba T, Yoshida H, Nakamura T, Inoue H, Ogawa Y, Tanaka M, Miyahara Y, Suganami T.
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Journal Title
Commun. Biol.
Volume: 3
Issue: 1
Pages: 313-313
DOI
Related Report
Peer Reviewed / Open Access
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