Role of the G-protein-coupled receptors that sense an extracellular pH in a bone and a joint function

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591157
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Meiji University (2011); Gunma University (2009-2010)
• Principal Investigator: TOMURA Hideaki 明治大学, 農学部, 准教授 (70217553)
• Project Period (FY): 2009 – 2011
• Keywords: シグナル伝達 / 骨 / プロトン / G蛋白共役型受容体 / 生理活性

Research Abstract

Extracellular acidification has great influence on a bone and a joint function. Extracellular acidification is occurred at the inflammation parts of arthritis and rheumatism and could have influence on the progression of these diseases. The inflammation responses of macrophages play an important role in the progression of these diseases. In this research, we showed that the G-protein-coupled receptors, which sense an extracellular pH, participate in the inflammation responses of macrophages. The result obtained in this research offers a new knowledge to understand the molecular mechanisms of the progression of these diseases.

Research Products

• [Journal Article] Involvement of proton-sensing receptor TDAG8 in the anti-inflammatory actions of dexamethasone in peritoneal macrophages (2011)
  • Author(s): He, XD., Tobo, M., Mogi, C., Nakakura, T., Komachi, M., Murata, N., Takano, M., Tomura, H., Sato, K. & Okajima, F
  • Journal Title: Biochem Biophys Res Commun Volume: 415 Pages: 627-631
  • Peer Reviewed
• [Journal Article] Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells (2011)
  • Author(s): Matsuzaki, S., Ishizuka, T., Yamada, T., Kamide, Y., Hisada, T., Ichimonji, I., Aoki, H., Yatomi, M., Komachi, M., Tsurumaki, H., Ono, A., Koga, Y., Dobashi, K., Mogi, C., Sato, K., Tomura, H., Mori, M. & Okajima, F.
  • Journal Title: Biochem Biophys Res Commun Volume: 413 Pages: 499-503
  • Peer Reviewed
• [Journal Article] Constituitively active heat shock factor 1 enhances glucose-driven insulin secretion (2011)
  • Author(s): Uchiyama, T., Tomono, S., Utsugii, T., Ohyama, Y., Nakamura, T., Tomura, H., Kawazu, S., Okajima, F. & Kurabayashi, M.
  • Journal Title: Metabolism Volume: 60 Pages: 789-798
  • Peer Reviewed
• [Journal Article] Lysophosphatidic Acid Inhibits CC Chemokine Ligand 5/RANTES Production by Blocking IRF-1-Mediated Gene Transcription in Human Bronchial Epithelial Cells (2010)
  • Author(s): Matsuzaki, S., Ishizuka, T., Hisada, T., Aoki, H., Komachi, M., Ichimonji, I., Utsugi, M., Ono, A., Koga, Y., Dobashi, K., Kurose, H., Tomura, H., Mori, M. & Okajima, F.
  • Journal Title: J Immunol. Volume: 185 Pages: 4863-4872
  • Peer Reviewed
• [Journal Article] Extracellular acidification stimulates IL-6 production and Ca(2+) mobilization through proton-sensing OGR1 receptors in human airway smooth muscle cells (2010)
  • Author(s): Ichimonji, I., Tomura, H., Mogi, C., Sato, K., Aoki, H., Hisada, T., Dobashi, K., Ishizuka, T., Mori, M. & Okajima, F.
  • Journal Title: Am J Physiol Lung Cell Mol Physiol Volume: 299 Pages: L567-577
  • Peer Reviewed
• [Journal Article] Ovarian cancer G protein-coupled receptor 1-dependent and-independent vascular actions to acidic pH in human aortic smooth muscle cells (2010)
  • Author(s): Liu, JP., Komachi, M., Tomura, H., Mogi, C., Damirin, A., Tobo, M., Takano, M., Nochi, H., Tamoto, K., Sato, K. & Okajima, F.
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 299 Pages: H731-742
  • Peer Reviewed
• [Journal Article] Each one of certain histidine residues in G-protein-coupled receptor GPR4 is critical for extracellular proton-induced stimulation of multiple G-protein-signaling pathways (2010)
  • Author(s): Liu, JP., Nakakura, T., Tomura, H., Tobo, M., Mogi, C., Wang, JQ., He, XD., Takano, M., Damirin, A., Komachi, M., Sato, K. & Okajima, F.
  • Journal Title: Pharmacol Res Volume: 61 Pages: 499-505
  • Peer Reviewed
• [Journal Article] Mechanism and role of high density lipoprotein-induced activation of AMP-activated protein kinase in endothelial cells (2010)
  • Author(s): Kimura, T., Tomura, H., Sato, K., Ito, M., Matsuoka, I., Im, DS., Kuwabara, A., Mogi, C., Itoh, H., Kurose, H., Murakami, M. & Okajima, F.
  • Journal Title: J Biol Chem Volume: 285 Pages: 4387-4397
  • Peer Reviewed
• [Journal Article] Role of Rap 1B and tumor suppressor PTEN in the negative regulation of lysophosphatidic acid-induced migration by isopreterenol in glioma cells (2009)
  • Author(s): Malchinkhuu, E., Sato, K., Maehama, T., Ishiuchi, S., Yoshimoto, Y., Mogi, C., Kimura, T., Kurose, H., Tomura, H. & Okajima, F.
  • Journal Title: M Biol Cell Volume: 20 Pages: 156-165
  • Peer Reviewed
• [Journal Article] Signaling pathways involved in DNA synthesis and migration in response to lysophosphatidic acid and low-density lipoprotein in coronary artery smooth muscle cells (2009)
  • Author(s): Komachi, M., Damirin, A., Malchinkhuu, E., Mogi, C., Tobo, M., Ohta, H., Sato, K., Tomura, H. & Okajima, F.
  • Journal Title: Vascul Pharmacol Volume: 50 Pages: 178-184
  • Peer Reviewed
• [Journal Article] Inhibition of superoxide anion production by extracellular acidification in neutrophils (2009)
  • Author(s): Murata, N., Mogi, C., Tobo, M., Nakakura, T., Sato, K., Tomura, H. & Okajima, F.
  • Journal Title: Cell Immunol Volume: 259 Pages: 21-26
  • Peer Reviewed
• [Journal Article] Involvement of proton-sensing TDAG8 in extracellular acidification-induced inhibition of proinflammatory cytokine production in peritoneal macrophages (2009)
  • Author(s): Mogi, C., Tobo, M., Tomura, H., Murata, N., He, XD., Sato, K., Kimura, T., Ishizuka, T., Sasaki, T., Sato, T., Kihara, Y., Ishii, S., Harada, A. & Okajima, F.
  • Journal Title: J Immunol Volume: 182 Pages: 3243-3251
  • Peer Reviewed
• [Presentation] 酸性ストレスによる血管平滑筋細胞からのプロスタサイクリン産生機構 (2011)
  • Author(s): 戸村秀明
  • Organizer: 第38回日本神経内分泌学会
  • Place of Presentation: 都道府県会館(東京)
  • Year and Date: 20111123-26
• [Presentation] 低pH条件下における血管平滑筋細胞からのプロスタサイクリン産生応答に対するプロトン感知性GPCRの関与 (2011)
  • Author(s): 戸村秀明
  • Organizer: 第104回日本繁殖生物学会
  • Place of Presentation: いわて県民情報交流センター・アイーナ(岩手)
  • Year and Date: 20110915-17
• [Presentation] 生理活性物質とシグナル伝達に関する最近の話題 (2011)
  • Author(s): 戸村秀明
  • Organizer: 第26回日本下垂体研究会
  • Place of Presentation: せとうち児島ホテル(岡山)
  • Year and Date: 20110826-27
• [Presentation] Each one of specified histidine residues in GPR4 is important for acidic pH-induced stimulation of multiple signaling pathways (2010)
  • Author(s): 戸村秀明
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド(兵庫)
  • Year and Date: 2010-12-07
• [Presentation] プロトンをセンスするGタンパク共役型受容体の情報変換機構と生体機能 (2010)
  • Author(s): 戸村秀明
  • Organizer: 第52回日本脂質生化学会
  • Place of Presentation: 伊香保(群馬)
  • Year and Date: 2010-06-14
• [Presentation] ヒト大動脈平滑筋細胞における細胞外プロトン/OGR1受容体を介したシクロオキシゲナーゼ2の発現のリゾホスファチジン酸による増加 (2009)
  • Author(s): 戸村秀明
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 神戸ポートアイランド(兵庫)
  • Year and Date: 20091021-24
• [Presentation] マウスマクロファージの酸性下での炎症性サイトカインの産生低下におけるTDAG8の関与 (2009)
  • Author(s): 戸村秀明
  • Organizer: 第80回日本動物学会
  • Place of Presentation: 静岡グランドシップ(静岡)
  • Year and Date: 20090917-20