生体バリアと細胞極性形成の制御機構

• 研究課題/領域番号: 19590398
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 実験病理学
• 研究機関: 札幌医科大学
• 研究代表者: 千葉 英樹 札幌医科大学, 医学部, 准教授 (00295346)
• 研究分担者: 澤田 典均 札幌医科大学, 医学部, 教授 (30154149) ; 稲富 周一郎 札幌医科大学, 医学部, 研究員 (10437999)
• 研究期間 (年度): 2007 – 2008
• 研究課題ステータス: 完了 (2008年度)
• 配分額: 4,550千円 (直接経費: 3,500千円、間接経費: 1,050千円); 2008年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円); 2007年度: 2,860千円 (直接経費: 2,200千円、間接経費: 660千円)
• キーワード: 病理学 / 細胞・組織 / 核内受容体 / 細胞極性 / 細胞間接着装置

研究概要

ビタミンD受容体ノックアウト(VDRKO)マウスの腸組織とビタミンD_3依存性ヒト腸上皮細胞株を用いて、活性型ビタミンD_3がVDRを介して、腸上皮におけるタイト結合分子claudin-2及びclaudin-12の発現を誘導することを見出した。また、これらのclaudinsが腸上皮細胞間でカルシウムイオン(Ca^<2+>)の細胞間隙チャネルを形成し、Ca^<2+>の通過を制御することを突き止めた。本研究は、カルシウム代謝に新規の知見を加え、骨粗鬆症やカルシウム代謝異常に対する新たな予防・治療戦略になることが期待される。

研究成果

• [雑誌論文] Knockdown of tight junction protein claudin-2 prevents bile canalicular formation in WIF-B9 cells (2009)
  • 著者名/発表者名: Son S, Kojima T, Decaens C, Yamaguchi H, Ito T, Imamura M, Murata M, Tanaka S, Chiba H, Hirata K, Sawada N
  • 雑誌名: Histochem Cell Biol 131 ページ: 411-424
  • 査読あり
• [雑誌論文] Knockdown of tight junction protein claudin-2 prevents bile canalicular formation in WIF-B9 cells. (2009)
  • 著者名/発表者名: Son S, et al.
  • 雑誌名: Histochem Cell Biol 131 ページ: 411-424
  • 査読あり
• [雑誌論文] Transmembrane proteins of tight junctions (2008)
  • 著者名/発表者名: Chiba H, Osanai M, Murata M, Kojima T, Sawada N
  • 雑誌名: BBA-Biomembranes 1778 ページ: 588-600
  • 査読あり
• [雑誌論文] Transforming growth factor-β induces epithelial to mesenchymal transition by down-regulation of claudin-1 expression and the fence function in adult rat hepatocytes (2008)
  • 著者名/発表者名: Kojima T, Takano K, Yamamoto T, Imamura M, Murata M, Son S, Yamaguchi H, Osanai M, Chiba H, Himi T, Sawada N
  • 雑誌名: Liver Int 28 ページ: 534-545
  • 査読あり
• [雑誌論文] Cdx2 transcription factor regulates claudin-3 and claudin-4 expression during intestinal differentiation of gastric carcinoma (2008)
  • 著者名/発表者名: Satake S, Semba S, Matsuda Y, Usami Y, Chiba H, Sawada N, Kasuga M, Yokozaki H
  • 雑誌名: Pathol Int 58 ページ: 156-163
  • NAID: 10027375982
  • 査読あり
• [雑誌論文] Hypermethylation-modulated downregulation of claudin-7 expression promotes the progression of colorectal carcinoma (2008)
  • 著者名/発表者名: Nakayama F, Semba S, Usami Y, Chiba H, Sawada N, Yokozaki H
  • 雑誌名: Pathobiology 75 ページ: 177-185
  • NAID: 120001408357
  • 査読あり
• [雑誌論文] Expression of tight junction proteins in epithelium including Ck20-positive M-like cells of human adenoids in vivo and in vitro (2008)
  • 著者名/発表者名: Takano K, Kojima T, Ogasawara N, Go M, Kikuchi S, Ninomiya T, Kurose M, Koizumi J, Kamekura R, Murata M, Tanaka S, Chiba H, Himi T, Sawada N
  • 雑誌名: J Mol Histol 39 ページ: 265-273
  • 査読あり
• [雑誌論文] Wnt signaling acts and is regulated in a human osteoblast differentiation dependent manner (2008)
  • 著者名/発表者名: Eijken M, Meijer IM, Westbroek I, Koedam M, Chiba H, Uitterlinden AG, Pols HA, van Leeuwen JP
  • 雑誌名: J Cell Biochem 104 ページ: 568-579
  • 査読あり
• [雑誌論文] Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca^<2+> absorption between enterocytes (2008)
  • 著者名/発表者名: Fujita H, Sugimoto K, Inatomi S, Maeda T, Osanai M, Uchiyama Y, Yamamoto Y, Wada T, Kojima T, Yokozaki H, Yamashita T, Kato S, Sawada N, Chiba H
  • 雑誌名: Mol Biol Cell 19 ページ: 1912-1921
  • 査読あり
• [雑誌論文] Protein kinase C enhances tight junction barrier function of human nasal epithelial cells in primary culture by transcriptional regulation (2008)
  • 著者名/発表者名: Koizumi J, Kojima T, Ogasawara N, Kamekura R, Kurose M, Go M, Harimaya A, Murata M, Osanai M, Chiba H, Himi T, Sawada N
  • 雑誌名: Mol Pharmacol 74 ページ: 432-442
  • 査読あり
• [雑誌論文] Experimental effect of retinoic acids on apoptosis during the development of diabetic retinopathy (2008)
  • 著者名/発表者名: Nishikiori N, Osanai M, Chiba H, Kojima T, Inatomi S, Ohguro H, Sawada N
  • 雑誌名: Clinical Ophthalmology 2 ページ: 233-235
  • 査読あり
• [雑誌論文] Evidence for multiple peroxisome proliferator-activated receptor gamma transcripts in bone : Fine-tuning by hormonal regulation and mRNA stability (2008)
  • 著者名/発表者名: Bruedigam C, Koedam M, Chiba H, Eijken M, van Leeuwen JP
  • 雑誌名: FEBS Lett 582 ページ: 1618-1624
  • 査読あり
• [雑誌論文] IGF-I regulates tight-junction protein claudin-1 during differentiation of osteoblast-like MC3T3-E1 cells via a MAP-kinase pathway (2008)
  • 著者名/発表者名: Hatakeyama N, Kojima T, Iba K, Murata M, Thi MM, Spray DC, Osanai M, Chiba H, Ishii S, Yamashita T, Sawada N
  • 雑誌名: Cell Tissue Res 334 ページ: 243-254
  • 査読あり
• [雑誌論文] Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca^<2+>absorption between enterocytes. (2008)
  • 著者名/発表者名: Fujita H, et al.
  • 雑誌名: Mol Biol Cell 19 ページ: 1912-1921
  • 査読あり
• [雑誌論文] Protein kinase C enhances tight junction barrier function of human nasal epithelial cells in primary culture by transcriptional regulation. (2008)
  • 著者名/発表者名: Koizumi J, et al.
  • 雑誌名: Mol Pharmacol 74 ページ: 432-442
  • 査読あり
• [雑誌論文] IGF-I regulates tight-junction protein claudin-1 during differentiation of osteoblast-like MC3T3-E1 cells via a MAP-kinase pathway. (2008)
  • 著者名/発表者名: Hatakeyama N, et al.
  • 雑誌名: Cell Tissue Res 334 ページ: 243-254
  • 査読あり
• [雑誌論文] Expression of tight junction proteins in epithelium including Ck20-positive M-like cells of human adenoids in vivo and in vitro. (2008)
  • 著者名/発表者名: Takano K, et al.
  • 雑誌名: J Mol Histol 39 ページ: 265-273
  • 査読あり
• [雑誌論文] Transforming growth factor-β induces epithelial to mesenchymal transition by down-regulation of claudin-1 expression and the fencefunction in adult rat hepatocytes. (2008)
  • 著者名/発表者名: Kojima T, et al.
  • 雑誌名: Liver Int 28 ページ: 534-545
  • 査読あり
• [雑誌論文] Experimental effect of retinoic acids on apoptosis during the development of diabetic retinopathy. (2008)
  • 著者名/発表者名: Nishikiori N, et al.
  • 雑誌名: Clinical ophthalmology 2 ページ: 233-235
  • 査読あり
• [雑誌論文] Hypermethylation-modulated downregulation of claudin-7 expression promotes the progression of colorectal carcinoma. (2008)
  • 著者名/発表者名: Nakayama F, et al.
  • 雑誌名: Pathobiology 75 ページ: 177-185
  • 査読あり
• [雑誌論文] Cdx2 transcription factor regulates claudin-3 and claudin-4 expression during intestinal differentiation of gastric carcinoma. (2008)
  • 著者名/発表者名: Satake S, et al.
  • 雑誌名: Pathol Int 58 ページ: 156-163
  • 査読あり
• [雑誌論文] Wnt signaling acts and is regulated in a human osteoblast differentiation dependent manner. (2008)
  • 著者名/発表者名: Eijken M, et al.
  • 雑誌名: J Cell Biochem 104 ページ: 568-579
  • 査読あり
• [雑誌論文] Evidence for multiple peroxisorae proliferator-activated receptor gamma transcripts in bone : Fine-tuning by hormonal regulation and mRNA stability. (2008)
  • 著者名/発表者名: Bruedigam C, et al.
  • 雑誌名: FEBS Lett 582 ページ: 1618-1624
  • 査読あり
• [雑誌論文] Transmembrane proteins of tight junctions. (2008)
  • 著者名/発表者名: Chiba H, et al.
  • 雑誌名: BBA-Biomembranes 1778 ページ: 588-600
  • 査読あり
• [雑誌論文] Transmembrane proteins of tight junctions. (2008)
  • 著者名/発表者名: Chiba H, et. al.
  • 雑誌名: BBA-Biomembranes 1778 ページ: 588-600
  • 査読あり
• [雑誌論文] Cdx2 transcription factor regulates claudin-3 and claudin-4 expression during intestinal differentiation of gastric carcinoma. (2008)
  • 著者名/発表者名: Satake S, et. al.
  • 雑誌名: Pathol Int 58 ページ: 156-163
  • 査読あり
• [雑誌論文] Experimental effect of retinoic acids on apoptosis during the development of diabetic retinopathy. (2008)
  • 著者名/発表者名: Nishikiori N, et. al.
  • 雑誌名: Clinical Ophthalmology 2 ページ: 1-3
  • 査読あり
• [雑誌論文] Cellular retinoic acid bioavailability determines epithelial integrity : role of retinoic acid receptor alpha agonists in colitis (2007)
  • 著者名/発表者名: Osanai M, Nishikiori N, Murata M, Chiba H, Kojima T, Sawada N
  • 雑誌名: Mol Pharmacol 71 ページ: 250-258
  • 査読あり
• [雑誌論文] Expression patterns of claudin family of tight-junction proteins in the mouse prostate (2007)
  • 著者名/発表者名: Sakai N, Chiba H, Fujita H, Akashi Y, Osanai M, Kojima T, Sawada N
  • 雑誌名: Histochem Cell Biol 127 ページ: 457-462
  • 査読あり
• [雑誌論文] Heterogeneous expression of claudin-4 in human colorectal cancer : decreased claudin-4 expression at the invasive front correlates cancer invasion and metastasis (2007)
  • 著者名/発表者名: Ueda J, Semba S, Chiba H, Sawada N, Seo Y, Kasuga M, Yokozaki H
  • 雑誌名: Pathobiology 74 ページ: 32-41
  • 査読あり
• [雑誌論文] Inhibitory effects of retinoic acid receptor alpha stimulants on murine cataractogenesis through suppression of deregulated calpains (2007)
  • 著者名/発表者名: Nishikiori N, Osanai M, Chiba H, Kojima T, Ohguro H, Sawada N
  • 雑誌名: Invest Ophth Vis Sci 48 ページ: 2224-2229
  • 査読あり
• [雑誌論文] Glial cell-derived cytokines attenuate the breakdown of vascular integrity in diabetic retinopathy (2007)
  • 著者名/発表者名: Nishikiori N, Osanai M, Chiba H, Kojima T, Mitamura Y, Ohguro H, Sawada N
  • 雑誌名: Diabetes 56 ページ: 1333-1340
  • 査読あり
• [雑誌論文] A novel monoclonal antibody against second extracellular loop of occludin disrupts epithelial cell polarity (2007)
  • 著者名/発表者名: Tokunaga Y, Kojima T, Osanai M, Murata M, Chiba H, Tobioka H, Sawada N
  • 雑誌名: J Histochem Cytochem 55 ページ: 735-744
  • 査読あり
• [雑誌論文] Oncostatin M induces upregulation of claudin-2 in rodent hepatocytes coinciding with changes in morphology and function of tight junctions (2007)
  • 著者名/発表者名: Imamura M, Kojima T, Lan M, Son S, Murata M, Osanai M, Chiba H, Hirata K, Sawada N
  • 雑誌名: Exp Cell Res 313 ページ: 1951-1962
  • 査読あり
• [雑誌論文] Gastric and intestinal claudins expression at the invasive front of gastric carcinoma (2007)
  • 著者名/発表者名: Matsuda Y, Semba S, Ueda J, Fuku T, Hasuo T, Chiba H, Sawada N, Kuroda Y, Yokozaki H
  • 雑誌名: Cancer Sci 98 ページ: 1014-1019
  • 査読あり
• [雑誌論文] Occludin-mediated premature senescence is a fail-safe mechanism against tumorigenesis in breast carcinoma cells (2007)
  • 著者名/発表者名: Osanai M, Murata M, Nishikiori N, Chiba H, Kojima T, Sawada N
  • 雑誌名: Cancer Sci 98 ページ: 1027-1034
  • NAID: 120002187916
  • 査読あり
• [雑誌論文] Epigenetic silencing of claudin-6 promotes anchorage-independent growth of breast carcinoma cells (2007)
  • 著者名/発表者名: Osanai M, Murata M, Chiba H, Kojima T, Sawada N
  • 雑誌名: Cancer Sci 98 ページ: 1557-1562
  • NAID: 10019997370
  • 査読あり
• [雑誌論文] Changes of gap and tight junctions during differentiation of human nasal epithelial cells using primary human nasal epithelial cells and primary human nasal fibroblast cells in a noncontact coculture system (2007)
  • 著者名/発表者名: Koizumi J, Kojima T, Kamekura R, Kurose M, Harimaya A, Murata M, Osanai M, Chiba H, Himi T, Sawada N
  • 雑誌名: J Membr Biol 218 ページ: 1-7
  • 査読あり
• [雑誌論文] Induction of claudins in passaged hTERT-transfected human nasal epithelial cells with an extended life span (2007)
  • 著者名/発表者名: Kurose M, Kojima T, Koizumi J, Kamekura R, Ninomiya T, Murata M, Ichimiya S, Osanai M, Chiba H, Himi T, Sawada N
  • 雑誌名: Cell Tissue Res 330 ページ: 63-74
  • 査読あり
• [雑誌論文] Expression patterns of claudin family of tight-junction proteins in the mouse prostate. (2007)
  • 著者名/発表者名: Sakai N, et. al.
  • 雑誌名: Histochem Cell Biol 127 ページ: 457-462
  • 査読あり
• [雑誌論文] Cellular retinoic acid bioavailability determines epithelial integrity: Role of retinoic acid receptor alpha agonists in colitis. (2007)
  • 著者名/発表者名: Osanai M, et. al.
  • 雑誌名: Mol Pharmacol 71 ページ: 250-258
  • 査読あり
• [雑誌論文] Heterogeneous expression of claudin-4 in human colorectal cancer: decreased claudin-4 expression at the invasive front correlates cancer invasion and metastasis. (2007)
  • 著者名/発表者名: Ueda J, et. al.
  • 雑誌名: Pathobiology 74 ページ: 32-41
  • 査読あり
• [雑誌論文] Inhibitory effects of retinoic acid receptor alpha stimulants on murine cataractogenesis through suppression of deregulated calpains. (2007)
  • 著者名/発表者名: Nishikiori N, et. al.
  • 雑誌名: Invest Ophthalmol Vis Sci 48 ページ: 2224-2229
  • 査読あり
• [雑誌論文] Glial cell-derived cytokines attenuate the breakdown of vascular integrity in diabetic retinopathy. (2007)
  • 著者名/発表者名: Nishikiori N, et. al.
  • 雑誌名: Diabetes 56 ページ: 1333-1340
  • 査読あり
• [雑誌論文] A novel monoclonal antibody against the second extracellular loop of occludin disrupts epithelial cell polarity. (2007)
  • 著者名/発表者名: Tokunaga Y, et. al.
  • 雑誌名: J Histochem Cytochem 55 ページ: 735-744
  • 査読あり
• [雑誌論文] Oncostatin M induces upregulation of claudin-2 in rodent hepatocytes coinciding with changes in morphology and function of tight junctions. (2007)
  • 著者名/発表者名: Imamura M, et. al.
  • 雑誌名: Exp Cell Res 313 ページ: 1951-1962
  • 査読あり
• [雑誌論文] Gastri can intestinal claudin expression at the invasive front of gastric carcinoma. (2007)
  • 著者名/発表者名: Matsuda Y, et. al.
  • 雑誌名: Cancer Sci 98 ページ: 1014-1019
  • 査読あり
• [雑誌論文] Occludin-mediated premature senescence is a fail-safe mechanism against tumorigenesis in breast carcinoma cells. (2007)
  • 著者名/発表者名: Osanai M, et. al.
  • 雑誌名: Cancer Sci 98 ページ: 1027-1034
  • 査読あり
• [雑誌論文] Epigenetic silencing of claudin-6 promotes anchorage-independent growth of breast carcinoma cells. (2007)
  • 著者名/発表者名: Osanai M, et. al.
  • 雑誌名: Cancer Sci 98 ページ: 1557-1562
  • 査読あり
• [雑誌論文] Changes of gap and tight junctions during differentiation of human nasal epithelial cells using primary human nasal epithelial cells and primary human nasal fibroblast cells in a noncontact coculture system. (2007)
  • 著者名/発表者名: Koizumi J, et. al.
  • 雑誌名: J Membr Biol 218 ページ: 1-7
  • 査読あり
• [雑誌論文] Induction of claudins in passaged hTERT-transfected human nasal epithelial cells with an extended life span. (2007)
  • 著者名/発表者名: Kurose M, et. al.
  • 雑誌名: Cell Tissue Res 330 ページ: 63-74
  • 査読あり
• [雑誌論文] Tight junction proteins and signal transduction pathways in hepatocytes
  • 著者名/発表者名: Kojima T, Murata M, Yamamoto T, Lan M, Imamura M, Son S, Takano K-i, Yamaguchi H, Ito T, Tanaka S, Chiba H, Hirata K, Sawada N
  • 雑誌名: Histol Histopathol (in press)
  • 査読あり
• [雑誌論文] Tight junction proteins and signal transduction pathways in hepatocytes
  • 著者名/発表者名: Koiima T, et. al
  • 雑誌名: Histol Histopathol (in press)
  • 査読あり
• [雑誌論文] Hypermethylation-modulated downregulation of claudin-7 expression promotes the progression of colorectal carcinoma.
  • 著者名/発表者名: Nakayama F, et. al.
  • 雑誌名: Pathobiology (in press)
  • 査読あり
• [雑誌論文] Expression of tight junction proteins in epithelium including Ck20-positive M-like cells of human adenoids in vivo and in vitro.
  • 著者名/発表者名: Takano K, et. al.
  • 雑誌名: J Mol Hist (in press)
  • 査読あり
• [雑誌論文] Wnt signaling acts and is regulated in a human osteoblast differentiation dependent manner.
  • 著者名/発表者名: Eijken M, et. al.
  • 雑誌名: J Cell Biochem (in press)
  • 査読あり
• [雑誌論文] Tight junction proteins claudin-2 and-12 are critical for vitamin D-dependent Ca^<2+> absorption between enterocytes.
  • 著者名/発表者名: Fujita H, et. al.
  • 雑誌名: Mol Biol Cell (in press)
  • 査読あり
• [雑誌論文] PKC enhances tight junction barrier function of human nasal epithelial cells in primary culture by transcriptional regulation.
  • 著者名/発表者名: Koizumi J, et. al.
  • 雑誌名: Mol Pharmacol (in press)
  • 査読あり
• [雑誌論文] TGF-β induces epithelial to mesenchymal transition by downregulation of claudin-1 expression and the fence function in adult rat hepatocytes.
  • 著者名/発表者名: Kojima T, et. al.
  • 雑誌名: Liver Int (in press)
  • 査読あり
• [学会発表] 細胞間接着と極性形成の制御機構 (2007)
  • 著者名/発表者名: 千葉英樹
  • 学会等名: 第53回日本病理学会秋期特別総会
  • 発表場所: 東京
  • 年月日: 2007-12-06
• [学会発表] A novel mechanism underlying vitamin D-dependent Ca^<2+> absorption between enterocytes (2007)
  • 著者名/発表者名: Chiba H
  • 学会等名: In : 4th meeting Bone Biology Forum
  • 発表場所: Shizuoka
• [学会発表] 核内受容体hepatocyte nuclear factor 4alphaは微絨毛と細胞接着の形成を誘導するモルフォルゲンとして働く (2007)
  • 著者名/発表者名: 千葉英樹, 村田雅樹, 小山内誠, 二宮孝文, 小島隆, 澤田典均
  • 学会等名: ワークショップ「細胞接着・細胞外基質・細胞間相互作用」第40回日本発生生物学会・第59回日本細胞生物学会大会
  • 発表場所: 福岡
• [学会発表] A novel mechanism underlying vitamin D-dependent Ca^<2+> absorption between enterocytes. (2007)
  • 著者名/発表者名: 千葉英樹, 他
  • 学会等名: In: 4th meeting bone biology forum
  • 発表場所: 静岡