Analysis of regulation of nuclear receptor-mediated signal transdidian by the ligand-specific transporters
| Project/Area Number |
18570104
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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 |
Structural biochemistry
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| Research Institution | Shinshu University (2007)
Niigata University (2006) |
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Principal Investigator |
FUJII Hiroshi Shinshu University, Faculty of Apiculture, Professor (90165340)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBATA Mnoru Niigata Univasity, Medical and Dalai Hospital, Professor (50196432)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,110,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | signal transduction / gene / regulation of expression / fatty acid / bile acid / lipid / nuclear receptor / transporter |
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| Research Abstract |
To elucidate function of ligand-specific transporters in the nuclear receptor (FXR: farnesoid X receptor or PPAR: peroxysome proliferator-activated receptor)-mediated signal transduction, we have tried to identify and analyze molecular mechanisms of a novel signal transduction mediated by PPAR or FXR.
1. Analysis of nuclear receptor FXR-mediated signal transduction:
During the course of studies, we have revealed that bile acid transporters (FABP6/I-BABP, IBAT) and FXR are co-localized in the rat ovary. These genes are expressed during the ovary differentiation. Furthermore, we have demonstrated that human OSBa/β gene is up-regulated by FXR and nuclear receptor LXR (liver X receptor) (Pharmaceutical Res. 24:390-398, 2007)
2. Analysis of nuclear receptors PPAR/FXR-mediated signal transduction in carcinogenesis or metastasis:
We have found that the nuclear receptor PPAR target gene, FABP-5 (C-FABP: cutaneous fatty acid-binding protein), is up-regulated in human malignant prostate or breast cancers and that is involved in metastasis in these tumors. Down-regulation of FABP-5 by its siRNA caused decrease in the incidence of cancer metastasis (Mt. J. Oncol. 32:767-775, 2008). Furthermore, we have demonstrated that FABP6 is up-regulated in human colorectal cancers (Clin. Cancer Res. 12 (17):5090-5095, 2006).
3. Analysis of novel PPAR-mediated signal transduction:
We have found that FABP5 and FABP7 (B-FABP) are specifically expressed in the growth cone in the rat brain important for the neurodegeneration and regeneration process. We have introduced siRNA for each FABP to analyze their functions in the growth cone. Furthermore, we have tried to examine specific proteins interacting with FABP5 or FABP7 using the immunoprecipitation assay.
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Report
(3 results)
Research Products
(30 results)
