Novel roles of lysolipid receptors : proton sensing and its biological function

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390016
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Gunma University
• Principal Investigator: OKAJIMA Fumikazu 群馬大学, 生体調節研究所, 教授 (30142748)
• Project Period (FY): 2009 – 2011
• Keywords: プロトン感知性受容体 / TDAG8 / OGR1 / 細胞外pH / 炎症性サイトカイン / マクロファージ / 血管平滑筋細胞 / 骨代謝

Research Abstract

The roles of proton-sensing GPCRs in inflammation, vascular biology, and bone remodeling in response to extracellular pH change were investigated. Our results suggested that TDAG8/Gs/cAMP is involved in the inhibition of inflammatory cytokine production and superoxide anion production in macrophages and neutrophils and OGR1 is in the stimulation of COX-2 expression in smooth muscle cells and osteoblast cells.

Research Products

• [Journal Article] An orally active lysophosphatidic acid receptor antagonist attenuates pancreatic cancer invasion and metastasis in vivo (2012)
  • Author(s): Komachi M, Sato K, Tobo M, Mogi C, Yamada T, Ohta H, Tomura H, Kimura T, Im DS, Yanagida K, Ishii S, Takeyoshi I, Okajima F.
  • Journal Title: Cancer Sci Volume: (in press)
  • 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 H, 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, and Okajima F.
  • Journal Title: Biophys Res Commun Volume: 413 Pages: 499-503
  • Peer Reviewed
• [Journal Article] Constitutively active heat shock factor 1 enhances glucose-driven insulin secretion (2011)
  • Author(s): Uchiyama T, Tomono S, Utsugi 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] Unmasking of LPA(1) receptor-mediated migration response to lysophosphatidic acid by interleukin-1 β-induced attenuation of Rho signaling pathways in rat astrocytes (2011)
  • Author(s): Sato K, Horiuchi Y, Jin Y, Malchinkhuu E, Komachi M, Kondo T, Okajima F.
  • Journal Title: J Neurochem Volume: 117 Pages: 164-174
  • Peer Reviewed
• [Journal Article] Role of sphingosine 1-phosphate in anti-atherogenic actions of high-density lipoprotein (2010)
  • Author(s): Sato K, Okajima F.
  • Journal Title: World J Biol Chem Volume: 1 Pages: 327-337
  • Peer Reviewed
• [Journal Article] Protective effect of resolvin E1 on the development of asthmatic airway inflammation (2010)
  • Author(s): Aoki H, Hisada T, Ishizuka T, Utsugi M, Ono A, Koga Y, Sunaga N, Nakakura T, Okajima F, Dobashi K, Mori M.
  • Journal Title: Biochem Biophys Res Commun Volume: 400 Pages: 128-133
  • Peer Reviewed
• [Journal Article] Lysophosphatidic acid inhibits CCL5/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 H, 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: 731-742
  • 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] Cross-talk Between Exogenous Statins and Endogenous High-density Lipoprotein in Anti-inflammatory and Anti-atherogenic Actions (2010)
  • Author(s): Kimura T, Sato K, Tomura H, Okajima F
  • Journal Title: Endocrine, Metabolic and Immune Disorder-Drug Targets (EMID-DT) Volume: 10 Pages: 8-15
  • 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 Rap1B and tumor suppressor PTEN in the negative regulation of lysophosphatidic acid-induced migration by isoproterenol 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: Mol Biol Cell Volume: 20 Pages: 5156-5165
  • Peer Reviewed
• [Journal Article] MInhibition 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] Increase in sphingolipid catabolic enzyme activity during aging (2009)
  • Author(s): Sacket SJ, Chung HY, Okajima F, Im DS.
  • Journal Title: Acta Pharmacol Sin Volume: 30 Pages: 1454-1461
  • 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, 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] 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, Tomura H, Malchinkhuu E, Tobo M, Mogi C, Yamada T, Kimura T, Kuwabara A, Ohta H, Im DS, Kurose H, Takeyoshi I, Sato K, Okajima F
  • Journal Title: Carcinogenesis Volume: 30 Pages: 457-465
  • 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: Vasc Pharmacol Volume: 50 Pages: 178-184
  • Peer Reviewed
• [Journal Article] Anti-atherogenic actions of high-density lipoprotein through sphingosine 1-phosphate receptors and scavenger receptor class B type I (2009)
  • Author(s): Okajima F, Sato K, Kimura T
  • Journal Title: Endocrine J Volume: 56 Pages: 315-332
  • Peer Reviewed
• [Presentation] プロトン感知性Gタンパク質共役型受容体OGR1の気管支喘息における関与について、 (2011)
  • Author(s): 青木悠, 茂木千尋, 久田剛志, 岩崎靖樹, 鶴巻寛朗, 山田秀典, 石塚全, 土橋邦生, 岡島史和, 森昌朋
  • Organizer: 第61回日本アレルギー学会秋季学術大会
  • Place of Presentation: グランドプリンスホテル新高輪国際館パミール(東京)
  • Year and Date: 20111110-12
• [Presentation] OGR1ファミリ.GPCRによるプロトン感知機構とその機能 (2011)
  • Author(s): 岡島史和
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都)
  • Year and Date: 20110921-24
• [Presentation] 血漿ならびにリポ蛋白質HDL中スフィンゴシン1-リン酸濃度調節におけるABCA1トランスポーターの役割 (2011)
  • Author(s): 佐藤幸市, 茂木千尋, 岡島史和
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都)
  • Year and Date: 20110921-24
• [Presentation] ク質共役型受容体細胞外pHを感知するGタンパ (2011)
  • Author(s): 岡島史和
  • Organizer: シンポジウムGタンパク質共役型受容体の日本薬学会第131年会シカッティングエッジ(紙上発表)
  • Place of Presentation: 静岡
  • Year and Date: 20110328-31
• [Presentation] ヒト膵臓癌細胞株のインビボ転移・浸潤に対するリゾホ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, 佐藤幸市, 茂木千尋, 当房雅之, 山田敬之, 戸村秀明, 岡島史和
  • Organizer: BMB2010第33回日本分子生物学会、第83回日本生化学会合同学会
  • Place of Presentation: 神戸ポートアイランド(神戸)
  • Year and Date: 20101207-10
• [Presentation] 細胞外プロトンをセンスするGタンパク共役型受容体の情報交換機構と生体機能(シンポジウム) (2010)
  • Author(s): 戸村秀明, 茂木千尋, 当房雅之, 佐藤幸市, 岡島史和
  • Organizer: 第52回日本脂質生化学会
  • Place of Presentation: 森秋旅館(伊香保)
  • Year and Date: 20100614-15
• [Presentation] 抗動脈硬化性・抗炎症性作用におけるスタチンと高密度リポ蛋白質のクロストーク (2010)
  • Author(s): 岡島史和
  • Organizer: 日本薬学会第130年会シンポジウム血管病発症のシグナル伝達と新たな治療戦略
  • Place of Presentation: 岡山コンベンションセンター(岡山)
  • Year and Date: 20100328-30
• [Presentation] 細胞外プロトンをリガンドとするGタンパク質共役受容体の骨リモデリングにおける役割 (2009)
  • Author(s): 茂木千尋, 岡島史和
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 群馬県民会館(前橋)
  • Year and Date: 20090423-25
• [Remarks]
  • URL: http://imcr.showa.gunma-u.ac.jp/lab/signal/index.html