Pathobiology of the tight junction : from cell biology of paracellular pathway to bed-side

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390103
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Sapporo Medical University
• Principal Investigator: SAWADA Norimasa Sapporo Medical University, 医学部, 教授 (30154149)
• Co-Investigator(Kenkyū-buntansha): KOJIMA Takashi 札幌医科大学, 医学部, 准教授 (30260764) ; CHIBA Hideki 札幌医科大学, 医学部, 准教授 (00295346) ; TANAKA Satoshi 札幌医科大学, 医学部, 講師 (30374250) ; MURATA Masaki 札幌医科大学, 医学部, 助教 (10404592)
• Project Period (FY): 2007 – 2009
• Keywords: 糖尿病網膜症 / Ca吸収 / 鼻アレルギー / 膵管上皮 / 肝(黄疸) / タイト結合 / バリア機能 / サイトカイン

Research Abstract

Tight junctions are intercellular junctions sealing intercellular spaces at the apical end of the lateral cell membranes. Tight junctions regulate the passage of various substances, and also maintain the cell polarity. In this study, we examined regulation of tight junctions by vitamin D, and patho-physiological changes of a barrier function of tight junctions in hepatic cells and human nasal epithelial cells by various cytokines, and in endothelial cells forming blood retinal barrier under a diabetic condition.

Research Products

• [Journal Article] Thymic stromal lymphopoietin induces tight junction protein claudin-7 via NF-kappaB in dendritic cells. (2010)
  • Author(s): Kamekura R, Kojima T, Takashima A, Koizumi JI, Ogasawara N, Go M, Takano KI, Murata M, Tanaka S, Ichimiya S, Himi T, Sawada N
  • Journal Title: Histochem Cell Biol 133 Pages: 339-348
  • Peer Reviewed
• [Journal Article] Pulmonary collectins protect macrophages against pore-forming activity of Legionella pneumophila and suppress its intracellular growth. (2010)
  • Author(s): Sawada K, Ariki S, Kojima T, Saito A, Yamazoe M, Nishitani C, Shimizu T, Takahashi M, Mitsuzawa H, Yokota SI, Sawada N, Fujii N, Takahashi H, Kuroki Y
  • Journal Title: J Biol Chem 285 Pages: 8434-8443
  • Peer Reviewed
• [Journal Article] Oncogenic and cell survival properties of the retinoic acid metabolizing enzyme, CYP26A1. (2010)
  • Author(s): Osanai M, Sawada N, Lee GH
  • Journal Title: Oncogene 29 Pages: 1135-1144
  • Peer Reviewed
• [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] Tight junction proteins and signal transduction pathways in hepatocytes. (2009)
  • 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 24 Pages: 1463-1472
  • Peer Reviewed
• [Journal Article] Thymic stromal lymphopoietin enhances tight junction barrier function of human nasal epithelial cells. (2009)
  • Author(s): Kamekura R, Kojima T, Koizumi J, Ogasawara N, Kurose M, Go M, Harimaya A, Murata M, Tanaka S, Chiba H, Himi T, Sawada N
  • Journal Title: Cell Tissue Res 338 Pages: 283-293
  • Peer Reviewed
• [Journal Article] Expression and localization of tricellulin in human nasal epithelial cells in vivo and in vitro. (2009)
  • Author(s): Ohkuni T, Kojima T, Ogasawara N, Masaki T, Ninomiya T, Kikuchi S, Go M, Takano K, Himi T, Sawada N
  • Journal Title: Med Mol Morphol 42 Pages: 204-211
  • Peer Reviewed
• [Journal Article] Induction of JAM-A during differentiation of human THP-1 dendritic cells. (2009)
  • Author(s): Ogasawara N, Kojima T, Go M, Fuchimoto J, Kamekura R, Koizumi J, Ohkuni T, Masaki T, Murata M, Tanaka S, Ichimiya S, Himi T, Sawada N
  • Journal Title: Biochem Biophys Res Commun 389 Pages: 543-549
  • 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] 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] 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 thymic stromal lymphopoietin (TSLP) in allergic rhinitis : Induction of tight junction proteins in human nasal epithelial cells and dendritic cells by epithelial-derived TSLP. (2008)
  • Author(s): Kamekura R, Kojima T, Koizumi J, Ogasawara N, Kurose M, Takano K, Go M, Himi T, Sawada N
  • Journal Title: Inflammation and Regeneration 28 Pages: 160-165
  • 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] Tight junction proteins claudin-2 and-12 are critical for vitamin D-dependent Ca2+ 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] Transforming growth factor-βinduces 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] Prevention of murine experimental corneal trauma by epigenetic events regulating claudin 6 and claudin 9. (2008)
  • Author(s): Nishikiori N, Sawada N, Ohguro H
  • Journal Title: Jpn J Ophthalmol 52 Pages: 195-203
  • 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] 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] 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] 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 Ophthalmol 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 the 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 claudin 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] nduction 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] 肝細胞タイト結合, claudinと肝小葉. (2007)
  • Author(s): 小島隆, 村田雅樹, 澤田典均
  • Journal Title: 肝胆膵 55(1) Pages: 45-54
• [Journal Article] Connexins induce and maintain tight junctions in epithelial cells. (2007)
  • Author(s): Kojima T, Murata M, Go M, Spray DC, Sawada N
  • Journal Title: J Membr Biol 217 Pages: 13-19
  • Peer Reviewed
• [Presentation] 正常ヒト鼻粘膜上皮バリア調節機構へのTLRの関与. (2009)
  • Author(s): 大國毅, 小島隆, 小笠原徳子, 正木智之, 氷見徹夫, 澤田典均
  • Organizer: 第8回コネキシン研究会
  • Place of Presentation: 福岡
  • Year and Date: 20091126-20091128
• [Presentation] 新規タイト結合蛋白tricellulinのJun N-terminal kinase (JNK)経路を介した発現調節機構の解明. (2009)
  • Author(s): 小島隆, 澤田典均
  • Organizer: 第8回コネキシン研究会
  • Place of Presentation: 福岡
  • Year and Date: 20091126-20091128
• [Presentation] 核内受容体PPAR-γを介したヒト鼻粘膜におけるタイト結合の発現調節機構. (2009)
  • Author(s): 小笠原徳子, 小島隆, 郷充, 亀倉隆太, 大國毅, 正木智之, 村田雅樹, 田中敏, 千葉英樹, 氷見徹夫, 澤田典均
  • Organizer: 第98回日本病理学会
  • Place of Presentation: 京都
  • Year and Date: 20090501-20090503
• [Presentation] 膵癌細胞株のPKCシグナル異常におけるタイト結合蛋白の変化. (2009)
  • Author(s): 伊東竜哉, 小島隆, 山口洋志, 村田雅樹, 田中敏, 千葉英樹, 平田公一, 澤田典均
  • Organizer: 第98回日本病理学会
  • Place of Presentation: 京都
  • Year and Date: 20090501-20090503
• [Presentation] ヒト膵管上皮細胞培養系の確立とタイト結合蛋白claudinを標的とした膵癌治療基礎解析. (2009)
  • Author(s): 山口洋志, 小島隆, 伊東竜哉, 木村康利, 澤田典均, 平田公一
  • Organizer: 第40回日本膵臓学会
  • Place of Presentation: 東京
  • Year and Date: 2009-07-30
• [Presentation] 核内受容体PPAR-gammaを介したヒト鼻粘膜上皮細胞および樹状細胞のタイト結合の発現調節機構. (2008)
  • Author(s): 小笠原徳子, 小島隆, 郷充, 亀倉隆太, 澤田典均, 氷見徹夫
  • Organizer: 日本アレルギー学会
  • Place of Presentation: 東京
  • Year and Date: 20081127-20081130
• [Presentation] ヒト鼻粘膜におけるタイト結合蛋白tricellulinの発現調節 (2008)
  • Author(s): 大國毅, 小島隆, 亀倉隆太, 小笠原徳子, 菊池真, 二宮孝文, 氷見徹夫, 澤田典均
  • Organizer: 第40回日本臨床分子形態学学会
  • Place of Presentation: 福岡
  • Year and Date: 20081003-20081004
• [Presentation] 核内受容体PPAR-gammaを介したヒト鼻粘膜上皮細胞および樹状細胞のタイト結合の発現調節機構. (2008)
  • Author(s): 小笠原徳子, 小島隆, 郷充, 亀倉隆太, 澤田典均, 氷見徹夫
  • Organizer: 第29回日本炎症再生学会
  • Place of Presentation: 東京
  • Year and Date: 20080708-20080710
• [Presentation] タイト結合:すきまの細胞生物学からヒト病態へ (2008)
  • Author(s): 澤田典均
  • Organizer: 第21回日本外科感染症学会
  • Place of Presentation: 札幌
  • Year and Date: 2008-11-07
• [Presentation] 肝疾患の病態とタイト結合. (2007)
  • Author(s): 澤田典均, 村田雅樹, 小山内誠, 千葉英樹小島隆
  • Organizer: 第4回日本病理学会カンファレンス「肝疾患研究の最前線:現状と課題」
  • Place of Presentation: 旭川
  • Year and Date: 20070727-20070728
• [Presentation] 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.ワークショップ「細胞接着・細胞外基質・細胞間相互作用」 (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: 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: 20070528-20070530
• [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
• [Book] Gap and tight junctions in liver: composition, regulation, and function. The Liver: Biology and Pathobiology, 5th Edition, edited by Arias IM, et al. (2009)
  • Author(s): Kojima T, Sawada N, Yamaguchi H, Fort AG, Spray DC
  • Total Pages: 201-220
  • Publisher: Lippincott Williams&Wilkins, Philadelphia