小島　隆 (コジマ　タカシ)

写真a

所属

附属がん研究所 細胞科学部門

職名

教授
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学歴 【 表示 ／ 非表示 】

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    1985年

    岐阜大学  

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    1985年

    岐阜大学  

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学位 【 表示 ／ 非表示 】

  • 博士（医学）

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所属学協会 【 表示 ／ 非表示 】

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    American Society for Cell Biology

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    日本癌学会

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    米国細胞生物学会

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    The Japanese Cancer Association

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    Japan Society for Cell Biology

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  • 札幌医科大学   医学部 医学科 病理学第二講座 医学部医学科基礎医学部門講座病理学第二講座   助教授  

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研究キーワード 【 表示 ／ 非表示 】

  • 細胞生物学

  • 肝臓学

  • 実験病理学

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  • Glyceraldehyde-derived advanced glycation end-products preferentially induce VEGF expression and reduce GDNF expression in human astrocytes

    H Miyajima, M Osanai, H Chiba, N Nishikiori, T Kojima, K Ohtsuka, N Sawada

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ( ACADEMIC PRESS INC ELSEVIER SCIENCE )  330 ( 2 ) 361 - 366  2005年05月

    　概要を見る

    The blood-brain barrier (BBB) is a biological unit composed of capillary endothelial cells and astrocytes. Here we examined the effects of various types of advanced glycation end-products (AGEs) on astrocytes and BBB-forming endothelial cells. While no type of AGE we examined changed the permeability of endothelial sheets, glyceraldehyde-derived AGE induced VEGF expression most significantly in astrocytes. The expression of glial cell line-derived neurotrophic factor (GDNF), which reduces the vascular permeability, was decreased in the astrocytes by treatment with glyceraldehyde-derived AGE. These results indicate that glyceraldehyde-derived AGE is the biologically active substance for astrocytes by regulating the VEGF and GDNF expression, which is causally contributing to an increase in the permeability of the BBB. (c) 2005 Elsevier Inc. All rights reserved.

    DOI PubMed CiNii

  • p38 MAP-kinase regulates function of gap and tight junctions during regeneration of rat hepatocytes

    T Yamamoto, T Kojima, M Murata, K Takano, M Go, N Hatakeyama, H Chiba, N Sawada

    JOURNAL OF HEPATOLOGY ( ELSEVIER SCIENCE BV )  42 ( 5 ) 707 - 718  2005年05月

    　概要を見る

    Background/Aims: Hepatocyte regeneration is considered to be associated with adaptive changes in expression of gap and tight junctions through multiple signal transduction pathways including p38 MAP-kinase. The role of the stress responsitive MAP-kinase, p38 MAP-kinase, signaling pathway in function of gap and tight junctions was examined during regeneration of rat hepatocytes in vivo and in vitro. Methods: We examined changes in formation, expression and function of gap and tight junctions in rat livers after 70% partial hepatectomy and in primary cultures of rat hepatocytes, by using a p38 MAP-kinase inhibitor, SB203580. Results: When p38 MAP-kinase was activated during partial hepatectomy, down-regulation of Cx32 and up-regulation of claudin-1 were observed. By SB203580 treatment, the down-regulation of Cx32 was inhibited and the up-regulation of claudin-1 was enhanced, well maintaining the structures of gap and tight junctions. SB203580 treatment did not affect the increase of hepatocyte proliferation. In EGF induced proliferative rat hepatocytes treated with SB203580, the expression and function of Cx32 and claudin-1 were increased. Conclusions: Dynamic changes of formation of gap and tight junctions during regeneration of rat hepatocytes in vivo and in vitro are in part controlled via a p38 MAP-kinase signaling pathway, and are independent of cell growth. © 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

    DOI

  • Activation of p21 (CIP1/WAF1) gene expression and inhibition of cell proliferation by overexpression of hepatocyte nuclear factor-4 alpha

    H Chiba, T Itoh, S Satohisa, N Sakai, H Noguchi, M Osanai, T Kojima, N Sawada

    EXPERIMENTAL CELL RESEARCH ( ELSEVIER INC )  302 ( 1 ) 11 - 21  2005年01月

    　概要を見る

    The F9 murine embryonal carcinoma cell line provides an attractive system for studying epithelial differentiation and antiproliferative processes. We have recently established F9 cells expressing doxycycline-inducible hepatocyte nuclear factor (HNF)-4alpha and shown that HNF-4alpha triggers the gene expression of tight-junction molecules, occludin, claudin-6, and claudin-7, as well as formation of functional tight junctions and polarized epithelial morphology (Exp. Cell Res. 286, [2003] 288). Since these events were very similar to those induced by retinoids, we investigated whether HNF-4alpha, like retinoid receptors, was involved in the control of cell proliferation. We herein show that HNF-4alpha up-regulates expression of the p21 gene, but not the p15, p16, p18, p19, or p27 gene, in a p53-independent manner, and inhibits cell growth in F9 cells. Similar results were observed in rat lung endothelial cells, in which expression of HNF-4alpha is conditionally induced by doxycycline. Furthermore, we demonstrate, by reporter assay, that HNF-4alpha significantly elevates the transcriptional activity of the p21 promoter. Since, HNF-4alpha is expressed not only in the liver but also in organs containing epithelial cells, such as kidney, intestine, pancreas, and stomach, it might also play critical roles in the regulation of epithelial morphogenesis and proliferation in these organs. (C) 2004 Elsevier Inc, All rights reserved.

    DOI PubMed CiNii

  • HLA-DR- and CD11c-positive Dendritic Cells Penetrate beyond Well-developed Epithelial Tight Junctions in Human Nasal Mucosa of Allergic Rhinitis.

    J Histochem Cytochem   53   611 - 9  2005年

    DOI

  • Oncogenic Raf-1 regulates epithelial to mesenchymal transition via distinct signal transduction pathways in an immortalized mouse hepatic cell line

    MD Lan, T Kojima, M Osanai, H Chiba, N Sawada

    CARCINOGENESIS ( OXFORD UNIV PRESS )  25 ( 12 ) 2385 - 2395  2004年12月

    　概要を見る

    The epithelial to mesenchymal transition (EMT) is considered to be an important event during malignant tumor progression and metastasis. Although Raf/MEK/ERK signaling causes EMT, the mechanisms, including the signaling pathways, are as yet unclear. In the present study we have examined the effects of signal transduction pathways on oncogenic Raf-1-induced EMT, using an immortalized mouse hepatic cell line. Oncogenic Raf-1-induced EMT is characterized by down-regulation of adherens and tight junctions and the reorganization of actin. An active Raf-1 gene was introduced into a mouse hepatic cell line which was then treated with the MAP kinase inhibitor PD98059, the p38 MAP kinase inhibitor SB203580, the PI3 kinase inhibitor LY294002 or the c-Src tyrosine kinase inhibitor PP2. The expression and localization of the adherens and tight junction proteins E-cadherin, occludin, ZO-1, claudin-1 and claudin-2 were determined by western blotting, RT-PCR and immunocytochemistry. The barrier function of tight junctions was assessed by measurements of transepithelial electric resistance (TER) and permeability in terms of fluxes of [C-14]mannitol and [C-14]inulin. In Raf-1-transfected cells expression of occludin and claudin-2 was markedly down-regulated at the protein and mRNA levels and the TER value was decreased, while the permeability was increased. The distribution of ZO-1, pancadherin and F-actin was changed from linear to zipper-like structures at cell borders. In Raf-1-transfected cells treated with PD98059 and SB203580, but not LY294002, expression and localization of claudin-2, but not occludin, recovered, together with barrier function, measured as the TER value. The distributions of ZO-1, pancadherin and F-actin also recovered on treatment with PD98059 and SB203580, but not LY294002. Expression and localization of occludin recovered slightly on treatment with PP2. Thus, oncogenic Raf-1 regulates EMT via distinct MAP kinase, p38 MAP kinase and c-Src tyrosine kinase signal pathways in the mouse hepatic cell line.

    DOI

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受賞 【 表示 ／ 非表示 】

  • 秋山財団 一般助成

    2005年  

  • 日本臨床分子形態学会論文賞

    2005年  

  • 日本臨床電子顕微鏡学会奨励賞

    2004年  

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共同研究・競争的資金等の研究課題 【 表示 ／ 非表示 】

  • 肝細胞におけるギャップおよびタイト結合蛋白の発現調節機構の解析

  • 耳鼻科領域におけるギャップおよびタイト結合と疾患

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