Functional roles of OSM in the development of NAFLD-NASH-HCC progression and its potential as a therapeutic target
| Project/Area Number |
17H02177
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied health science
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
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| Keywords | メタボリック症候群 / 非アルコール性脂肪肝炎 / 肝硬変 / 肝癌 / サイトカイン |
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| Outline of Final Research Achievements |
One week of high-fructose diet (HFrD) feeding induced hepatic steatosis as well as high-fat diet (HFD) feeding in C57BL/6J mice. The lipid droplets in hepatocytes of HFrD-fed mice were larger than those of HFD-fed mice. In addition, the expressions of CIDEa and CIDEc, important regulators of lipid storage by promoting the fusion of lipid droplets, were increased in the liver of HFrD-fed mice compared to those in HFD-fed mice. The expression of the neutrophil marker (neutrophil elastase) increased in the liver of the HFD-fed and the HFrD-fed mice. When HFrD was fed, lipid droplets in hepatocytes of OSMRβ-deficient (OSMRKO) mice were larger than those in wild-type (WT) mice. The expressions of CIDEc and neutrophil elastase increased in the liver of OSMRKO mice compared to those in WT mice. These results suggest that OSM may modulate the development of fructose-induced NASH through inhibiting the fusion of lipid droplets and neutrophil-induced inflammation.
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| Academic Significance and Societal Importance of the Research Achievements |
NAFLDやNASH、及びそれらが増悪して発症する肝硬変、肝癌に対しては確立された治療法がない。近年、NAFLDやNASHの発症には脂肪よりも果糖の過剰摂取が重要であることが明らかとなり、その分子機構が注目されている。本研究では、果糖によるNASH発症機構に対して、OSMが関与する可能性が示唆された。以前に我々は、NAFLDの発症をOSMが抑制するという知見を得ており、NAFLD-NASHという一連の病態のいずれにおいてもOSMが何らかの役割を担っている可能性が示唆された。OSMシグナリングの制御はこれらの疾患やそれらが増悪して発症する肝硬変、肝癌の新規治療薬の候補となる可能性が考えられる。
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Report
(4 results)
Research Products
(6 results)
