2000 Fiscal Year Final Research Report Summary
Genetic control of apoptosis in developing pulmonary fibrosis
| Project/Area Number |
11670591
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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 |
Respiratory organ internal medicine
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
SETOGUCHI Yasuhiro Juntendo Univ. Medicine, Assist, Prof., 医学部・内科, 講師 (90206649)
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| Co-Investigator(Kenkyū-buntansha) |
SEINO Kenichiro Tsukuba Univ. Surgery Assist, Prof., 医学専門学群, 講師 (20312845)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Pulmonary fibrosis / apeptosis / Gene transfer / Gene therapy / Fas / Fas-L / FADD / Adenovirus vecror |
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| Research Abstract |
Upregulation of Fas and FasL expression in bronchiolar and alveolar epithelial cells Was found in patients with pulmonary fibrosis. In Bleomycin-treated experimental animal, apoptosis in lung tissue through the interaction of Fas-FasL contributes to development of pulmonary fibrosis. Fag are cell surface molecules that trigger apoptosis or inflammation upon engagement by specific receptor or antibody. FADD is recruited to the cytoplasmic domain of these receptors upon their activation and works as common mediator to induce apoptosis. Based upon these knowledge, we hypothesized that intracellular signals through Fas modified to be dominant-negative signal would suppress the development of pulmonary fibrosis. Tb evaluate this hypothesis, we constructed recombinant adenovirus vector coding FADD deletion mutant lacking the death effector domain. Bleomycin-induced pulmonary fibrosis was partially ameliorated by intratracheal FADD dominant negative transduction. This result would provide the basis for a novel therapeutic modality in pulmonary fibrosis.
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Research Products
(16 results)
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[Publications] Seino K, Setoguchi Y, Ogino T, Kayagaki N, Akiba H, Taniguchi H, Takada Y, Todoroki T, Fukuchi Y, Yagita H, Okumura K, Fukao K.: "Protection against Fas- and tumor necrosis factor receptor 1-mediated liver injury by blockade of FADD without. loss of NF-kB activation."(Ann Surg). (Inpress) (2001)
Description
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