| Project/Area Number |
18K08216
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Osaka City University |
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Principal Investigator |
Morioka Tomoaki 大阪市立大学, 大学院医学研究科, 准教授 (30382154)
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| Co-Investigator(Kenkyū-buntansha) |
塩井 淳 大阪市立大学, 大学院看護学研究科, 教授 (90260801)
庄司 哲雄 大阪市立大学, 大学院医学研究科, 准教授 (40271192)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | サルコペニア / オンコスタチンM / 骨格筋萎縮 / STAT3 / 慢性腎臓病 / C2C12細胞 / 腎不全 / アデニン負荷 / C/EBPδ |
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| Outline of Final Research Achievements |
In this study, we investigated the role of oncostatin M (OSM) in the pathogenesis of sarcopenia associated with chronic kidney disease. The mouse model of kidney failure induced by adenine exhibited reduced skeletal muscle mass with increased expression of OSM and OSM receptor and increased expression of genes associated with muscle degradation and growth inhibition. Next, in mature C2C12 myotubes treated with OSM in vitro, the myotube size was reduced, the expression of genes related to myogenic differentiation was decreased, while the expression of genes related to muscle degradation was increased. Furthermore, the effects of OSM on myotube size and changes in the gene expression were attenuated by pretreatment with an STAT3 inhibitor or siRNA-mediated STAT3 knockdown in C2C12 myotubes.
These results suggest that OSM contributes to muscle atrophy in chronic kidney disease by inhibiting myogenic differentiation and activating muscle degradation in a STAT3-dependent manner.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により，炎症性サイトカインに属する多機能蛋白オンコスタチンMが慢性腎臓病に伴うサルコペニアに関与すること，またその機序の一部が細胞レベルで明らかになった．
慢性腎臓病患者の予後に関わるサルコペニアの機序としては，多様な要因が想定されている．今回，その一つとしてオンコスタチンMの役割が明らかになったことで，慢性腎臓病患者のサルコペニアを抑制し，予後改善につながる治療への発展が期待される．
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