Regulation of biological barrier and cell polarity formation

2008 Fiscal Year Final Research Report

• Project/Area Number: 19590398
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Sapporo Medical University
• Principal Investigator: CHIBA Hideki Sapporo Medical University, 医学部, 准教授 (00295346)
• Co-Investigator(Kenkyū-buntansha): SAWADA Norimasa 札幌医科大学, 医学部, 教授 (30154149) ; INATOMI Syuichiro 札幌医科大学, 医学部, 研究員 (10437999)
• Project Period (FY): 2007 – 2008
• Keywords: 病理学 / 細胞・組織 / 核内受容体 / 細胞極性 / 細胞間接着装置

Research Abstract

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。

Research Products

• [Journal Article] Knockdown of tight junction protein claudin-2 prevents bile canalicular formation in WIF-B9 cells (2009)
  • Author(s): Son S, Kojima T, Decaens C, Yamaguchi H, Ito T, Imamura M, Murata M, Tanaka S, Chiba H, Hirata K, Sawada N
  • Journal Title: Histochem Cell Biol 131 Pages: 411-424
  • Peer Reviewed
• [Journal Article] Transmembrane proteins of tight junctions (2008)
  • Author(s): Chiba H, Osanai M, Murata M, Kojima T, Sawada N
  • Journal Title: BBA-Biomembranes 1778 Pages: 588-600
  • Peer Reviewed
• [Journal Article] 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)
  • Author(s): Kojima T, Takano K, Yamamoto T, Imamura M, Murata M, Son S, Yamaguchi H, Osanai M, Chiba H, Himi T, Sawada N
  • Journal Title: Liver Int 28 Pages: 534-545
  • Peer Reviewed
• [Journal Article] Cdx2 transcription factor regulates claudin-3 and claudin-4 expression during intestinal differentiation of gastric carcinoma (2008)
  • Author(s): Satake S, Semba S, Matsuda Y, Usami Y, Chiba H, Sawada N, Kasuga M, Yokozaki H
  • Journal Title: Pathol Int 58 Pages: 156-163
  • Peer Reviewed
• [Journal Article] Hypermethylation-modulated downregulation of claudin-7 expression promotes the progression of colorectal carcinoma (2008)
  • Author(s): Nakayama F, Semba S, Usami Y, Chiba H, Sawada N, Yokozaki H
  • Journal Title: Pathobiology 75 Pages: 177-185
  • Peer Reviewed
• [Journal Article] Expression of tight junction proteins in epithelium including Ck20-positive M-like cells of human adenoids in vivo and in vitro (2008)
  • Author(s): 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
  • Journal Title: J Mol Histol 39 Pages: 265-273
  • Peer Reviewed
• [Journal Article] Wnt signaling acts and is regulated in a human osteoblast differentiation dependent manner (2008)
  • Author(s): Eijken M, Meijer IM, Westbroek I, Koedam M, Chiba H, Uitterlinden AG, Pols HA, van Leeuwen JP
  • Journal Title: J Cell Biochem 104 Pages: 568-579
  • Peer Reviewed
• [Journal Article] Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca^<2+> absorption between enterocytes (2008)
  • Author(s): 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
  • Journal Title: Mol Biol Cell 19 Pages: 1912-1921
  • Peer Reviewed
• [Journal Article] Protein kinase C enhances tight junction barrier function of human nasal epithelial cells in primary culture by transcriptional regulation (2008)
  • Author(s): Koizumi J, Kojima T, Ogasawara N, Kamekura R, Kurose M, Go M, Harimaya A, Murata M, Osanai M, Chiba H, Himi T, Sawada N
  • Journal Title: Mol Pharmacol 74 Pages: 432-442
  • Peer Reviewed
• [Journal Article] Experimental effect of retinoic acids on apoptosis during the development of diabetic retinopathy (2008)
  • Author(s): Nishikiori N, Osanai M, Chiba H, Kojima T, Inatomi S, Ohguro H, Sawada N
  • Journal Title: Clinical Ophthalmology 2 Pages: 233-235
  • Peer Reviewed
• [Journal Article] Evidence for multiple peroxisome proliferator-activated receptor gamma transcripts in bone : Fine-tuning by hormonal regulation and mRNA stability (2008)
  • Author(s): Bruedigam C, Koedam M, Chiba H, Eijken M, van Leeuwen JP
  • Journal Title: FEBS Lett 582 Pages: 1618-1624
  • Peer Reviewed
• [Journal Article] IGF-I regulates tight-junction protein claudin-1 during differentiation of osteoblast-like MC3T3-E1 cells via a MAP-kinase pathway (2008)
  • Author(s): Hatakeyama N, Kojima T, Iba K, Murata M, Thi MM, Spray DC, Osanai M, Chiba H, Ishii S, Yamashita T, Sawada N
  • Journal Title: Cell Tissue Res 334 Pages: 243-254
  • Peer Reviewed
• [Journal Article] Cellular retinoic acid bioavailability determines epithelial integrity : role of retinoic acid receptor alpha agonists in colitis (2007)
  • Author(s): Osanai M, Nishikiori N, Murata M, Chiba H, Kojima T, Sawada N
  • Journal Title: Mol Pharmacol 71 Pages: 250-258
  • Peer Reviewed
• [Journal Article] Expression patterns of claudin family of tight-junction proteins in the mouse prostate (2007)
  • Author(s): Sakai N, Chiba H, Fujita H, Akashi Y, Osanai M, Kojima T, Sawada N
  • Journal Title: Histochem Cell Biol 127 Pages: 457-462
  • Peer Reviewed
• [Journal Article] Heterogeneous expression of claudin-4 in human colorectal cancer : decreased claudin-4 expression at the invasive front correlates cancer invasion and metastasis (2007)
  • Author(s): Ueda J, Semba S, Chiba H, Sawada N, Seo Y, Kasuga M, Yokozaki H
  • Journal Title: Pathobiology 74 Pages: 32-41
  • Peer Reviewed
• [Journal Article] Inhibitory effects of retinoic acid receptor alpha stimulants on murine cataractogenesis through suppression of deregulated calpains (2007)
  • Author(s): Nishikiori N, Osanai M, Chiba H, Kojima T, Ohguro H, Sawada N
  • Journal Title: Invest Ophth Vis Sci 48 Pages: 2224-2229
  • Peer Reviewed
• [Journal Article] Glial cell-derived cytokines attenuate the breakdown of vascular integrity in diabetic retinopathy (2007)
  • Author(s): Nishikiori N, Osanai M, Chiba H, Kojima T, Mitamura Y, Ohguro H, Sawada N
  • Journal Title: Diabetes 56 Pages: 1333-1340
  • Peer Reviewed
• [Journal Article] A novel monoclonal antibody against second extracellular loop of occludin disrupts epithelial cell polarity (2007)
  • Author(s): Tokunaga Y, Kojima T, Osanai M, Murata M, Chiba H, Tobioka H, Sawada N
  • Journal Title: J Histochem Cytochem 55 Pages: 735-744
  • Peer Reviewed
• [Journal Article] Oncostatin M induces upregulation of claudin-2 in rodent hepatocytes coinciding with changes in morphology and function of tight junctions (2007)
  • Author(s): Imamura M, Kojima T, Lan M, Son S, Murata M, Osanai M, Chiba H, Hirata K, Sawada N
  • Journal Title: Exp Cell Res 313 Pages: 1951-1962
  • Peer Reviewed
• [Journal Article] Gastric and intestinal claudins expression at the invasive front of gastric carcinoma (2007)
  • Author(s): Matsuda Y, Semba S, Ueda J, Fuku T, Hasuo T, Chiba H, Sawada N, Kuroda Y, Yokozaki H
  • Journal Title: Cancer Sci 98 Pages: 1014-1019
  • Peer Reviewed
• [Journal Article] Occludin-mediated premature senescence is a fail-safe mechanism against tumorigenesis in breast carcinoma cells (2007)
  • Author(s): Osanai M, Murata M, Nishikiori N, Chiba H, Kojima T, Sawada N
  • Journal Title: Cancer Sci 98 Pages: 1027-1034
  • Peer Reviewed
• [Journal Article] Epigenetic silencing of claudin-6 promotes anchorage-independent growth of breast carcinoma cells (2007)
  • Author(s): Osanai M, Murata M, Chiba H, Kojima T, Sawada N
  • Journal Title: Cancer Sci 98 Pages: 1557-1562
  • Peer Reviewed
• [Journal Article] 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)
  • Author(s): Koizumi J, Kojima T, Kamekura R, Kurose M, Harimaya A, Murata M, Osanai M, Chiba H, Himi T, Sawada N
  • Journal Title: J Membr Biol 218 Pages: 1-7
  • Peer Reviewed
• [Journal Article] Induction of claudins in passaged hTERT-transfected human nasal epithelial cells with an extended life span (2007)
  • Author(s): Kurose M, Kojima T, Koizumi J, Kamekura R, Ninomiya T, Murata M, Ichimiya S, Osanai M, Chiba H, Himi T, Sawada N
  • Journal Title: Cell Tissue Res 330 Pages: 63-74
  • Peer Reviewed
• [Journal Article] Tight junction proteins and signal transduction pathways in hepatocytes
  • Author(s): 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
  • Journal Title: Histol Histopathol (in press)
  • Peer Reviewed
• [Presentation] A novel mechanism underlying vitamin D-dependent Ca^<2+> absorption between enterocytes (2007)
  • Author(s): Chiba H
  • Organizer: In : 4th meeting Bone Biology Forum
  • Place of Presentation: Shizuoka
  • Year and Date: 20070824-25
• [Presentation] 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)
  • Author(s): 千葉英樹, 村田雅樹, 小山内誠, 二宮孝文, 小島隆, 澤田典均
  • Organizer: 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
  • Place of Presentation: 福岡
  • Year and Date: 20070528-30
• [Presentation] 細胞間接着と極性形成の制御機構 (2007)
  • Author(s): 千葉英樹
  • Organizer: 第53回日本病理学会秋期特別総会
  • Place of Presentation: 東京
  • Year and Date: 2007-12-06