| Project/Area Number |
10670412
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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 |
内科学一般
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| Research Institution | Hiroshima University |
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Principal Investigator |
MAEDA Hiroyuki HIROSHIMA UNIV., MEDICAL HOSPITAL, RESEARCH ASSOCIATE, 医学部・附属病院, 助手 (80274075)
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| Co-Investigator(Kenkyū-buntansha) |
HIYAMA Keiko HIROSHIMA UNIV., FACULTY OF MEDICINE, RESEARCH ASSOCIATE, 医学部, 助手 (60253069)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | adenovirus vector / anti-sense RNA / PNAs / hTR / hTRT / 慢性関節リウマチ / リンパ球 / テロメラーゼ / PNA / アンチセンス / アデノウィルスベクター |
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| Research Abstract |
Telomerase is essential for the indefinite proliferation of human cells. And its activation plays a circle role in cellular immortality. We have shown that detection of telomerase activity in synovial tissues is useful for diagnosis of rheumatoid arthritis (RA). We also have shown that telomerase activity in RA synovial tissue is likely derived from infiltrating mononuclear cells and may be involved in the pathogenesis of RA and that the presence of tetomerase activity in RA may be an indicator of an aggressive phenotype.
We evaluated peptide nucleic acids, (PNAS) - mediated inhibition of telomerase activity in various cell lines. The antisense PNAS against a part of telomerase gene demonstrated little inhibitory effect on telomerase activity, indicating that cellular uptake might be a limiting factor.
Next, an adenovirus vector expressing antisense mRNA against a part of telomerase gene was constructed. Telomerase activities in various human cell lines infected with ,the vector were not inhibited. The result indicate that the construct of the vector needs to be further investigated.
Further, an adenovirus vector expressing lipocortin 1, an endogenous anti-inflammation mediator, was constructed. A549 cells infected with the vector showed reduced prostaglandin E2 production, which indicate the vector could mimic a part of actions of corticosteroid. Further exploration for new therapeutic strategy should be continued.
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