| Project/Area Number |
14207027
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Tohoku University |
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Principal Investigator |
NUKIWA Toshihiro Tohoku University Institute of Development, Aging and Cancer, Professor, 加齢医学研究所, 教授 (40129036)
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| Co-Investigator(Kenkyū-buntansha) |
SAIJO Yasuo Tohoku University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (10270828)
EBINA Masahito Tohoku University Hospital, Lecturer, 病院・講師 (10280885)
KIKUCHI Toshiaki Tohoku University Hospital, Assistant, 病院・助手 (10280926)
SUZUKI Takuji Tohoku University Hospital, Assistant, 病院・助手 (80344670)
MAEMONDO Makoto Tohoku University Hospital, Assistant, 病院・助手 (40344676)
萩原 弘一 東北大学, 医学部附属病院, 講師 (00240705)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥49,920,000 (Direct Cost: ¥38,400,000、Indirect Cost: ¥11,520,000)
Fiscal Year 2004: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
Fiscal Year 2003: ¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
Fiscal Year 2002: ¥21,320,000 (Direct Cost: ¥16,400,000、Indirect Cost: ¥4,920,000)
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| Keywords | HGF / SLPI / Bone marrow derived cells / Tissue repair / Tissue regeneration / Defense system / Knockout mouse / Lung carcinogenesis / LPS |
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| Research Abstract |
The number of patients with lung cancer or pulmonary inflammatory diseases has been increasing recently. In these diseases, the basic mechanisms of defense or regeneration must have been flawed due to in part aging process, and related to the pathophysiology or intractability of the diseases. The aim of this investigation is to analyze these mechanisms in the direction of hepatocyte growth factor (HGF) or secretory leukoprotease inhibitor (SLPI) in which we have been studying. The summary of the research achievements in these 3 years is as follows :
1)Antiprotease and non-antiprotease function of SLPI : phenatypic analyzes of the SLPI targeted mice :
Although the antiprotease phenotypes of the SLPI for wound healing or protective effect of proepithelin against neutrophil elastase are well analyzed, we found that SLPI-/-mice are vulnerable to LPS with response of high IL-6 production or suppression of IkB-beta expression in SLPI-/-macrophages. These phenomena are likely based on the non-antiprotease functions. Interestingly, lung carcinogenesis by urethane (1mg/g body wt) was suppressed in SLPI-/-mice. These facts indicate a need to analyze SLPI binding proteins for clarify non-antiproease activity of SLPI.
2)HGF suppresses the recruitment of bone marrow (BM) derived progenitor cells :
4 weeks after the transplantation of BM cells from GFP mice following whole body irradiation (6-10 Gy), the mice were treated using bleomycin with or without gene transfer of HGF. While incorporation of BM cells in the inflammatory lesions is enhanced, HGF rather suppressed the recruitment of BM cells in the bleomycin-induced lung injury. In the context that fibrocytes derived from BM cells promotes lung fibrosis, the suppressive effect of HGF for BM cells could be a novel function.
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