Analysis of regulation of nuclear receptor-mediated signal transdidian by the ligand-specific transporters

配体特异性转运蛋白对核受体介导的信号转导蛋白的调节分析

• 批准号: 18570104
• 负责人: FUJII Hiroshi
• 金额: $ 2.63万
• 依托单位: Shinshu University (2007)Niigata University (2006)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18570104/
• 关键词: signal transduction; gene; regulation of expression; fatty acid; bile acid; lipid; nuclear receptor; transporter

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.

为了阐明配体特异性转运蛋白在核受体(FXR：法尼西德X受体或PPAR：过氧化部分增殖物激活受体)介导的信号转导中的作用，我们试图鉴定和分析PPAR或FXR1介导的一种新的信号转导的分子机制。核受体FXR介导的信号转导分析：在研究过程中，我们发现胆汁酸转运体(FABP6/I-BABP，IBAT)和FXR在大鼠卵巢中是共定位的。这些基因在卵巢分化过程中表达。2.核受体β/FPAR介导的信号转导分析：我们发现核受体PPAR靶基因FABP-5(C-FABP：皮肤脂肪酸结合蛋白)在人类恶性前列腺癌或乳腺癌中表达上调，参与了这些肿瘤的转移。FABP-5的siRNA下调FABP-5导致癌症转移发生率下降(MT。J·奥科尔。32：767-775,2008)。此外，我们还证明了FABP6在人类结直肠癌(Clin.癌症研究12(17)：5090-5095,2006)。分析新的PPAR介导的信号转导：我们发现FABP5和FABP7(B-FABP)在大鼠脑内的生长锥中特异表达，在神经退化和再生过程中起重要作用。我们已经为每个FABP引入了siRNA来分析它们在生长锥中的功能。此外，我们还尝试用免疫沉淀法检测与FABP5或FABP7相互作用的特定蛋白。

项目成果

血中腸型脂肪酸結合蛋白測定による急性腸炎診断

血液肠脂肪酸结合蛋白测定诊断急性肠炎

• 发表时间: 2007

A natural PPAR-γ agonist, 15-deoxy-delta 12,14-prostaglandin J2, may act as an enhancer of PAI-1 in human proximal renal tubular cells under hypoxic and inflammatory conditions

• DOI: 10.1093/ndt/gfn139
• 发表时间: 2008-08-01
• 期刊: NEPHROLOGY DIALYSIS TRANSPLANTATION
• 影响因子: 6.1
• 作者: Kimura, Hideki;Li, Xuan;Yoshida, Haruyoshi
• 通讯作者: Yoshida, Haruyoshi

Establishment and characterization of monoclonal and polyclonal antibodies against human intestinal fatty acid-binding protein(I-FABP).

抗人肠脂肪酸结合蛋白（I-FABP）单克隆和多克隆抗体的建立和表征。

• 发表时间: 2008
• 期刊: J. Immunoassay & Immunochem 29
• 作者: H.L. Wong;R. Pinontoan;K. Hayashi;R. Tabata;T. Yaeno;K. Hasegawa;C. Kojima;H. Yoshioka;K. Iba;T. Kawasaki;K. Shimamoto;Y. Saito;H. L. Wong;Y.Tanaka;M.Mishima;Y.Tanaka;K.Furuita;児嶋長次郎;H. Kimura;E. A. Morgan;S. Kajiura
• 通讯作者: S. Kajiura

Expression of cutaneous fatty acid-binding protein (C-FABP) in prostate cancer: Potential prognostic marker and target for tumourigenecity-suppression

皮肤脂肪酸结合蛋白（C-FABP）在前列腺癌中的表达：潜在的预后标志物和肿瘤发生抑制的靶点

• 发表时间: 2008
• 期刊: Int. J. Oncol. 32
• 作者: H.L. Wong;R. Pinontoan;K. Hayashi;R. Tabata;T. Yaeno;K. Hasegawa;C. Kojima;H. Yoshioka;K. Iba;T. Kawasaki;K. Shimamoto;Y. Saito;H. L. Wong;Y.Tanaka;M.Mishima;Y.Tanaka;K.Furuita;児嶋長次郎;H. Kimura;E. A. Morgan;S. Kajiura;E.A. Morgan;S. Kajiura;H. Kimura;E. A. Morgan
• 通讯作者: E. A. Morgan

Development and evaluation of a new sandwich ELISA system for intestinal fatty acid Binding protein (I-FABP) concentrations in human serum

开发和评估人血清中肠脂肪酸结合蛋白 (I-FABP) 浓度的新型夹心 ELISA 系统

• 发表时间: 2007
• 期刊: Jpn. J. of Med. & Parmceut. Sci 58, 5
• 作者: H.L. Wong;R. Pinontoan;K. Hayashi;R. Tabata;T. Yaeno;K. Hasegawa;C. Kojima;H. Yoshioka;K. Iba;T. Kawasaki;K. Shimamoto;Y. Saito;H. L. Wong;Y.Tanaka;M.Mishima;Y.Tanaka;K.Furuita;児嶋長次郎;H. Kimura;E. A. Morgan;S. Kajiura;E.A. Morgan;S. Kajiura;H. Kimura;E. A. Morgan;S. Kajiura;X. Li;M. Okuwaki;舟岡 宏幸;X. Li;M. Okuwaki;H. Funaoka
• 通讯作者: H. Funaoka