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

• 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
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• 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 / Gタンパク共役受容体 / プロトン感知性GPCR / 炎症性サイトカイン / マウスマクロファージ / LPS / TDAG8 / cAMP

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] An orally active lysophosphatidic acid receptor antagonist attenuates panereatic cancer invasion and metastasis in vivo (2012)
  • Author(s): Komachi M
  • Journal Title: Cancer Science Volume: (印刷中) Issue: 6 Pages: 1099-1104
  • DOI: 10.1111/j.1349-7006.2012.02246.x
  • Peer Reviewed
• [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
  • 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
  • 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] 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
  • Journal Title: Am J Physiol Heart Circ Phtsiol Volume: 299
  • Peer Reviewed
• [Journal Article] Extracellular acidification stimulates IL-6 production and Ca(2+) mobiliwtion through proton-sensing OGR1 receptors in human airway smooth muscle cells (2010)
  • Author(s): Ichimonji I
  • Journal Title: Am J Physiol Lung Cell Mol Physiol Volume: 299
  • 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
  • Journal Title: J Immunol Volume: 185 Pages: 4863-4872
  • Peer Reviewed
• [Journal Article] Constituively active heat shock factor 1 enhances glucose-driven insulin secretion. (2010)
  • Author(s): Uchiyama T
  • Journal Title: Metabolism Volume: In press
  • Peer Reviewed
• [Journal Article] Cross-talk Between Exogenous Statins and Endogenous High-density Lipoprotein in Anti-inflammatory and Anti-atherogenic Actions. (2010)
  • Author(s): Kimura T
  • Journal Title: Endocrine, Metbolic and Immune Disorder-Drug Targets (In press)
  • 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 IP
  • Journal Title: Pharmacol Res (In press)
  • 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
• [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
  • Journal Title: Vasc Pharmacol 50 Pages: 178-184
  • Peer Reviewed
• [Journal Article] LPA_1 receptors mediate stimulation, whereas LPA_2 receptors mediate inhibition, of migration of pancreatic cancer cells in response to lysophosphatidic acid and malignant ascites. (2009)
  • Author(s): Komachi M
  • Journal Title: Carcinogenesis 30 Pages: 457-465
  • Peer Reviewed
• [Journal Article] Involvement of Proton-Sensing TDAG8 in Extracellular Acidification-Induced Inhibition of Pro-Inflammatory Cytokine Production In Peritoneal Macrophages. (2009)
  • Author(s): Mogi C
  • Journal Title: J Immunol 182 Pages: 3243-3251
  • Peer Reviewed
• [Journal Article] Inhibition of superoxide anion production by extracelluar acidification in neutrophils. (2009)
  • Author(s): Murata N
  • Journal Title: Cell Immunol 259 Pages: 21-26
  • Peer Reviewed
• [Journal Article] Role of Rap1B and Tumor Suppressor PTEN in the Negative Regulation of Lysophosphatidic Acid-induced Migration by Isoproterenol in Glioma Cells. (2009)
  • Author(s): Malchinkhuu E
  • Journal Title: Mol Biol Cell 20 Pages: 5156-5165
  • Peer Reviewed
• [Journal Article] Mechanism and role of high-density lipoprotein-indueed activation of AMP-activated protein kinase in endothelial cells. (2009)
  • Author(s): Kimura T
  • Journal Title: J Biol Chem 285 Pages: 1387-4397
  • Peer Reviewed
• [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: 岡山・せとうち児島ホテル
  • Year and Date: 2011-08-26
• [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)
• [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)
• [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)
• [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] インスリン分泌における細胞外pHの影響とOGR1の役割 (2010)
  • Author(s): 中倉敬
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2010-12-07
• [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(兵庫県)
  • Year and Date: 2010-12-07
• [Presentation] 糖質コルチコイドの抗炎症作用におけるTDAG8の役割 (2010)
  • Author(s): Xiaodong He
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2010-12-07
• [Presentation] ヒト膵臓癌細胞のインビボ転移・浸潤に対するリゾボスファチジン酸受容体アンタゴニストKi16198の抑制作用 (2010)
  • Author(s): 小町麻由美
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • 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] 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(群馬県)
  • Year and Date: 2010-06-14
• [Presentation] リゾフォスファチジン酸による血管内皮細胞のVEカドヘリンのトランスロケーション制御機構 (2010)
  • Author(s): 木村孝穂
  • Organizer: 第52回日本脂質生化学会
  • Place of Presentation: 伊香保(群馬県)
  • Year and Date: 2010-06-14
• [Presentation] Mechanism and role of high-density lipoprotein-induced cAMP-activated protein kinase activation in endothelial cells (2010)
  • Author(s): Takao Kimura
  • Organizer: International Symposium on Cardiovascular Endocrinology and Metabolism 2010
  • Place of Presentation: Nara, Japan
  • Year and Date: 2010-04-01
• [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)
• [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)
• [Presentation] ヒト大動脈血管平滑筋細胞のCOX-2発現/プロスタサイクリン産生応答におけるプロント感知性GPCRとLPA受容体のクロストーク (2009)
  • Author(s): 劉進朋
  • Organizer: 第51回日本脂質生化学会
  • Place of Presentation: ウィルあいち(愛知県女性総合センター:名古屋)
• [Presentation] LPA1 receptors and LPA2 receptors mediate stimulation and inhibition of migration of pancreatic cancer cells, respectively. (2009)
  • Author(s): Mayumi Komachi
  • Organizer: 21st IUBMB & 12th FAOBMB International Congress of Biochemistry and Molecular Biology
  • Place of Presentation: Shanghai China
• [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回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] ヒト膵臓癌細胞の遊走・浸潤におけるリゾホスファチジン酸受容体LPA2の役割について (2009)
  • Author(s): 小町麻由美
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
• [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回日本動物学会大会
  • Place of Presentation: 静岡グランシップ
• [Remarks]
  • URL: http://imcr.showa.gunma-u.ac.jp/lab/signal/index.html
• [Remarks]
  • URL: http://imcr.showa.gunma-u.ac.jp/lab/signal/index.html