Analysis of lipid mediator signaling that increases hyaluronic acid synthesis and the effect of lipid mediator on cell senescence

• Project/Area Number: 26860144
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: Ochanomizu University
• Principal Investigator: GOTOH Mari お茶の水女子大学, ヒューマンライフイノベーション研究所, 特任准教授 (80467050)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: ヒアルロン酸 / 環状ホスファチジン酸 / 繊維芽細胞 / 老化 / 加齢 / 線維芽細胞 / 生理活性脂質

Outline of Final Research Achievements

We have found that cyclic phosphatidic acid (cPA) has the function of promoting hyaluronic acid production on skin fibroblasts and synoviocyte. In this research project, we revealed that the expression of hyaluronan synthase 2 messenger RNA and protein is up-regulated by cPA treatment.
In addition, we clarified the mRNA expression of hyaluronic acid-related proteins in human skin fibroblasts from donors of various ages (range, 0.7-69 years). As a result, it was revealed that the exertion of hyaluronan synthase did not decrease also in aged cells.

Research Products

• [Journal Article] 2- O -Carba-oleoyl cyclic phosphatidic acid induces glial proliferation through the activation of lysophosphatidic acid receptor (2018)
  • Author(s): Nakajima Shingo、Gotoh Mari、Fukasawa Keiko、Murofushi Hiromu、Murakami-Murofushi Kimiko
  • Journal Title: Brain Research Volume: 1681 Pages: 44-51
  • DOI: 10.1016/j.brainres.2017.12.031
  • Peer Reviewed / Open Access
• [Journal Article] Quantitative determination of cyclic phosphatidic acid and its carba analog in mouse organs and plasma using LC-MS/MS (2018)
  • Author(s): Shimizu Yoshibumi、Ishikawa Masaki、Gotoh Mari、Fukasawa Keiko、Yamamoto Shinji、Iwasa Kensuke、Yoshikawa Keisuke、Murakami-Murofushi Kimiko
  • Journal Title: Journal of Chromatography B Volume: 1076 Pages: 15-21
  • DOI: 10.1016/j.jchromb.2018.01.002
  • Peer Reviewed / Open Access
• [Journal Article] LPA5 signaling is involved in multiple sclerosis-mediated neuropathic pain in the cuprizone mouse model (2018)
  • Author(s): Tsukahara Ryoko、Yamamoto Shinji、Yoshikawa Keisuke、Gotoh Mari、Tsukahara Tamotsu、Neyama Hiroyuki、Ishii Satoshi、Akahoshi Noriyuki、Yanagida Keisuke、Sumida Hayakazu、Araki Masatake、Araki Kimi、Yamamura Ken-ichi、Murakami-Murofushi Kimiko、Ueda Hiroshi
  • Journal Title: Journal of Pharmacological Sciences Volume: 136 Issue: 2 Pages: 93-96
  • DOI: 10.1016/j.jphs.2018.01.001
  • Peer Reviewed / Open Access
• [Journal Article] Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease (2017)
  • Author(s): Yamamoto S, Yamashina K, Ishikawa M, Gotoh M, Iwasa K, Yagishita S, Maruyama K, Murakami-Murofushi K, Yoshikawa K
  • Journal Title: Journal of Neuroinflammation Volume: 14 Issue: 1 Pages: 142-142
  • DOI: 10.1186/s12974-017-0923-5
  • Peer Reviewed / Open Access
• [Journal Article] Age-related changes in cyclic phosphatidic acid-induced hyaluronic acid synthesis in human fibroblasts (2017)
  • Author(s): Sano Katsura、Gotoh Mari、Dodo Kyoko、Tajima Noriaki、Shimizu Yoshibumi、Murakami-Murofushi Kimiko
  • Journal Title: Human Cell Volume: 31 Issue: 1 Pages: 72-77
  • DOI: 10.1007/s13577-017-0185-7
  • Peer Reviewed
• [Journal Article] Effect of cyclic phosphatidic acid on the proliferation and differentiation of mouse cerebellar granule precursor cells during cerebellar development (2015)
  • Author(s): Misa KONAKAZAWA, Mari GOTOH, Kimiko MURAKAMI-MUROFUSHI, Yasunori MIYAMOTO
  • Journal Title: Brain research Volume: 1614 Pages: 28-37
  • DOI: 10.1016/j.brainres.2015.04.013
  • Peer Reviewed / Open Access
• [Journal Article] Pattern Quantification from Human Skin Fibroblast Images: Image quantification for fibroblast characterization (2015)
  • Author(s): Md. Khayrul BASHAR, Kei HASHIMOTO, Kanako ENOYOSHI, Kimiko YAMASHITA, Mari GOTOH, Hiroshi KORI
  • Journal Title: Journal of Bioinformatics and Neuroscience Volume: 1 Pages: 31-37
  • DOI: 10.1109/iciibms.2015.7439540
  • Peer Reviewed / Open Access
• [Journal Article] 脂質メディエーター・環状ホスファチジン酸の変形性関節症と多発性硬化症への効果とその医療応用への展望 (2015)
  • Author(s): 後藤真里、吉川圭介、塚原涼子、室伏きみ子
  • Journal Title: 脂質栄養学 Volume: 24 Pages: 41-51
  • NAID: 130005068519
  • Acknowledgement Compliant
• [Journal Article] Cyclic phosphatidic acid and lysophosphatidic acid induce hyaluronic acid synthesis via CREB transcription factor regulation in human skin fibroblasts (2014)
  • Author(s): Katsura MAEDA-SANO†, Mari GOTOH†, Toshiro MOROHOSHI, Takao SOMEYA, Hiromu MUROFUSHI, Kimiko MURAKAMI-MUROFUSHI
  • Journal Title: Biochem Biophys Acta- Molecular and Cell Biology of Lipids Volume: 1841 Issue: 9 Pages: 1256-1263
  • DOI: 10.1016/j.bbalip.2014.05.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cyclic phosphatidic acid treatment suppress cuprizone-induced demyelination and motor dysfunction in mice (2014)
  • Author(s): Yamamoto S, Gotoh M, Kawamura Y, Yamashina K, Yagishita S, Awaji T, Tanaka M, Maruyama K, Murakami-Murofushi K, Yoshikawa K.
  • Journal Title: European Journal of Pharmacology Volume: 741 Pages: 17-24
  • DOI: 10.1016/j.ejphar.2014.07.040
  • Peer Reviewed / Open Access
• [Journal Article] Cyclic Phosphatidic Acid Relieves Osteoarthritis Symptoms (2014)
  • Author(s): Mari GOTOH†, Aya NAGANO†, Ryoko TSUKAHARA, Hiromu MUROFUSHI, Kimiko MURAKAMI-MUROFUSHI
  • Journal Title: Mol. Pain Volume: 10 Pages: 52-52
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Search for the most ‘primitive’ membranes and their reinforcers (2014)
  • Author(s): Yoichi NAKATANI, Nigel RIBEIRO, Stéphane STREIFF, Mari GOTOH, Gianluca POZZI, Laurent DÉSAUBRY, Alain MILON
  • Journal Title: Origins of Life and Evolution of Biospheres Volume: 44 Issue: 3 Pages: 197-208
  • DOI: 10.1007/s11084-014-9365-6
  • Peer Reviewed / Open Access
• [Presentation] Effect of lipid mediator, cyclic phosphatidic acid on osteoarthritis, and its future prospects in medical application (2017)
  • Author(s): Mari GOTOH
  • Organizer: 15th anniversary Unistra-Ochadai Workshop
• [Presentation] Analyzing Orientation Patterns of Human Skin Fibroblasts using Image Gradient Information (2017)
  • Author(s): Md. Khayrul BASHAR, Kei HASHIMOTO, Mari GOTOH, and Hiroshi KORI
  • Organizer: The 39th Annual International Conference of the IEEE Engineering in Medicine & Biology Society
  • Int'l Joint Research
• [Presentation] 穿刺脳損傷修復における生理活性脂質cPA誘導体(2ccPA)の機能解析 (2016)
  • Author(s): 濱野文菜、中島麻里、橋本恵、後藤真里、室伏きみ子、宮本泰則
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
• [Presentation] Aging effects on hyaluronan production in human skin fibroblasts (2016)
  • Author(s): Katsura SANO, Mari GOTOH, Kyoko DODO, Yoshibumi SHISMIZU, Noriaki TAJIMA, Kimiko MURAKAMI-MUROFUSHI
  • Organizer: The International Federation of Societies of Cosmetic Chemists (IFSCC2016)
  • Place of Presentation: アメリカ
  • Year and Date: 2016-10-30
  • Int'l Joint Research
• [Presentation] Cyclic phosphatidic acid derivative is a novel drug candidate for multiple scleosis (2016)
  • Author(s): Keisuke YOSHIKAWA, Shinji YAMAMOTO, Mari GOTOH, Yoshibumi SHIMIZU, M. Hashimoto, K. Yamashina, M. Suzuki, Kei MARUYAMA, Kimiko MURAKAMI-MUROFUSHI
  • Organizer: 14th Meeting of the Asian-Pacific Society for Neurochemistry (APSN)
  • Place of Presentation: スペイン
  • Year and Date: 2016-08-28
  • Int'l Joint Research
• [Presentation] Orientation Quantification of Human Skin Fibroblasts using HOG Feature Descriptor (2016)
  • Author(s): Khayrul BASHAR, Kei HASHIMOTO, Mari GOTOH, Hiroshi KORI
  • Organizer: The 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 2016)
  • Place of Presentation: アメリカ
  • Year and Date: 2016-08-16
  • Int'l Joint Research
• [Presentation] コラーゲンコートが皮膚線維芽細胞の渦状パターン形成に与える影響 (2016)
  • Author(s): 後藤真里、橋本恵、榎吉奏子、山下公子、郡宏
  • Organizer: 第48回 日本結合組織学会学術大会
  • Place of Presentation: 長崎
  • Year and Date: 2016-06-24
• [Presentation] 多発性硬化症の新規治療薬候補・環状ホスファチジン酸誘導体 (2016)
  • Author(s): 山本梓司、清水嘉文、後藤真里、橋本真歩、山科孝太、岩佐健介、丸山敬、室伏きみ子、吉川圭介
  • Organizer: 第58回 日本脂質生化学会
  • Place of Presentation: 秋田
  • Year and Date: 2016-06-09
• [Presentation] 2-Carba-cyclic phosphatidic acid, a chemically synthesized cyclic phosphatidic acid derivative, is a novel drug candidate for multiple sclerosis (2015)
  • Author(s): Shinji YAMAMOTO, Yoshibumi SHIMIZU, Mari GOTOH, Kei MARUYAMA, Kimiko MURAKAMI-MUROFUSHI, Keisuke YOSHIKAWA
  • Organizer: 第58回 日本神経化学会大会
  • Place of Presentation: 埼玉 大宮ソニックシティ
  • Year and Date: 2015-09-11
• [Presentation] LC-MS/MSによる環状ホスファチジン酸の定量法の確立 (2015)
  • Author(s): 清水嘉文、後藤真里、室伏擴、室伏きみ子
  • Organizer: 第21回 人間情報学会講演会
  • Place of Presentation: 東京 山上会館
  • Year and Date: 2015-09-10
• [Presentation] Cyclic phosphatidic acid treatment suppress cuprizone-induced demyelination and motor dysfunction in mice (2015)
  • Author(s): Shinji YAMAMOTO, Mari GOTOH, Yuuki KAWAMURA, Kota YAMASHINA, Sosuke YAGISHITA, Takeo AWAJI, Kei MARUYAMA, Kimiko MURAKAMI-MUROFUSHI, Keisuke YOSHIKAWA
  • Organizer: 6th International Conference on Phospholipase A2 and Lipid Mediators (PLM2015)
  • Place of Presentation: 東京
  • Year and Date: 2015-02-10 – 2015-02-12
• [Presentation] 環状ホスファチジン酸による皮膚線維芽細胞のヒアルロン酸合成促進作用と加齢への影響 (2014)
  • Author(s): 後藤真里、前田桂、塚原涼子、田島範明、室伏擴、室伏きみ子
  • Organizer: 第19回 人間情報学会講演会
  • Place of Presentation: 東京大学
  • Year and Date: 2014-12-02
• [Presentation] 変形性関節症（OA）における環状ホスファチジン酸（cPA） の効果の検討 (2014)
  • Author(s): 塚原涼子、後藤真里、長野あや、室伏擴、諸星俊郎、大塚一幸、室伏きみ子
  • Organizer: 第19回 人間情報学会講演会
  • Place of Presentation: 東京大学
  • Year and Date: 2014-12-02
• [Presentation] Cyclic phosphatidic acid induces hyaluronic acid synthesis via CREB transcription factor regulation in human skin fibroblasts (2014)
  • Author(s): 前田桂、後藤真里、室伏擴、室伏きみ子
  • Organizer: 第75回 SCCJ研究討論会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-28
• [Presentation] Cyclic phosphatidic acid induces hyaluronic acid synthesis via CREB transcription factor regulation in human skin fibroblasts (2014)
  • Author(s): Katsura MAEDA-SANO, Mari GOTOH, Kimiko MURAKAMI-MUROFUSHI
  • Organizer: The International Federation of Societies of Cosmetic Chemists forum (IFSCC 2014)
  • Place of Presentation: Paris
  • Year and Date: 2014-10-27 – 2014-10-30
• [Presentation] 環状ホスファチジン酸の真皮線維芽細胞への影響 (2014)
  • Author(s): 後藤真里
  • Organizer: 第5回 化粧品開発展 アカデミックフォーラム
  • Place of Presentation: 東京ビックサイト
  • Year and Date: 2014-10-20 – 2014-10-22
  • Invited
• [Presentation] Cyclic Phosphatidic Acid Relieves Osteoarthritis Symptoms (2014)
  • Author(s): Ryoko TSUKAHARA, Mari GOTOH, Aya NAGANO, Hiromu MUROFUSHI, Toshiro MOROHOSHI, Kimiko MURAKAMI-MUROFUSHI
  • Organizer: 第87回 日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] 環状ホスファチジン酸、リゾホスファチジン酸による皮膚線維芽細胞へのヒアルロン酸合成促進作用 (2014)
  • Author(s): 後藤真里、佐野桂、室伏擴、室伏きみ子
  • Organizer: 第56回 日本脂質生化学会
  • Place of Presentation: 大阪 近畿大学
  • Year and Date: 2014-06-06 – 2014-06-07