| Project/Area Number |
09557090
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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 | 展開研究 |
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| Research Field |
Kidney internal medicine
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| Research Institution | TOKYO MEDICAL AND DENTAL UNIVERSITY |
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Principal Investigator |
TERADA Yoshio Graduate School, TOKYO MEDICAL AND DENTAL UNIVERSITY, INSTRUCTOR, 大学院・医歯学総合研究科, 助手 (30251531)
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| Co-Investigator(Kenkyū-buntansha) |
TUJITA Yoshio SANKYO CO, LIMITED., DAIICHI-LABORATORY, VICE-DIRECTOR, 第一生物研究所, 所次長
辻田 代史雄 三共株式会社, 第一生物研究所, 所長
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1998: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1997: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | Adenovirus / cyclin / cell cycle / Glomerulonephritis / mesangial cell / cGMP / HMG-Coa inhibitor / glucocorticoid / 腎炎 / メザンギウム細胞 / アデノカイルス |
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| Research Abstract |
Recent studies have revealed that mitogen-actiated protein kinase(MAPK)consists of at least three subfamilies, namely include classical MAPK(also known as ERK), stress-activated protein kinase/c-Jun N-terminal kinase(JNK), and p38 kinase. TGF-b-activating kinase(TAK)-1 is a novel MAPKKK which is reported to stimulate p38K and/or JNK pathway. To elucidate functional roles of the TAK1 pathway, we transfected its constitutive active form(TAKdN)and negative form(TAKK63W)to LLCPK1 cells. TAKdN inhibited 3H-thymidine uptake, and reduced the percentages of S and G2/M phases. TAKK63W ameliorated inhibition of 3H-thymidine uptake and the percentages of S and G2/M phases by TGF-b. Western blot analysis demonstrates that the cyclin D1 protein level was negatively regulated by overexpression of TAKdN.Moreover, overexpression of TAKdN inhibited cyclin D1 promoter activity. In contract, constitutive active MKK1, the classical p42/44 MAPK-activator, increased cyclin D1 promoter activity and protein level. Overexpression of the active form of MKK1 increased 3H-thymidine uptake, while the inactive form decreased the uptake.
In conclusion, cyclin D1 promoter activity and cell cycle progression are negatively regulated by the TAK1-MKK6-p38K pathway and positively regulated by the MKK1-p42/44 MAPK pathway.
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