| Project/Area Number |
22591195
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Kansai Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ADACHI Yasushi 関西医科大学, 医学部, 非常勤講師 (10268336)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | マウス / ネフローゼ症候群 / NF-κB / Dehydroxy-methyl-epoxyquinomicin (DHMEQ) / DHMEQ / PAN / ICGNマウス / 遺伝性腎炎 / 骨髄内骨髄移植 / アルブミン尿 / アルブミン/クレアチニン比 / 腎炎 / 腎機能 / タンパク尿 |
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| Research Abstract |
Recent observations have revealed that the activation of nuclear factor κB (NF-κB) plays an important role in minimal- change nephrotic syndrome (MCNS), and there is a theory that therapeutic efficacy of steroids in MCNS is associated with the inhibition of NF-κB activity. Dehydroxy-methyl-epoxyquinomicin (DHMEQ) is a newly developed inhibitor of NF-κB that directly binds specifically to NF-κB components to inhibit DNA binding. Therefore, it is thought to be more specific than most other NF-κB inhibitors.
We conducted this study to determine whether DHMEQ may ameliorate puromycin aminonucleoside (PAN)-induced nephrosis in a murine model for MCNS. As a result, DHMEQ could reduce the albuminuria and ameliorate the hypercholesterolemia and hypoalbuminemia in comparison with PAN injection without DHMEQ in the mice. DHMEQ also inhibited PAN-induced NF-κB translocation from the cytoplasm to the nucleus. In conclusion, NF-κB plays an important role in the pathogenesis of MCNS, and these results suggest that DHMEQ is a candidate therapeutic agent for MCNS.
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