Functional expression of sensing foctors against maternal osmotic stress in the placenta

• Project/Area Number: 15K08595
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Keio University
• Principal Investigator: NISHIMURA Tomohiro 慶應義塾大学, 薬学部(芝共立), 准教授 (40453518)
• Co-Investigator(Kenkyū-buntansha): 登美 斉俊 慶應義塾大学, 薬学部(芝共立), 教授 (30334717)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 胎盤 / 胎児成長 / トランスポーター / アミノ酸 / 発現調節 / 胎児発育不全 / 浸透圧

Outline of Final Research Achievements

Placenta is an interface between mother and fetus and it has a role of nutrients transfer. The placenta has the function mitigating the osmotic stress exposed from maternal blood. Part of amino acid is transferred via amino acid transport system A from mother to fetus in the placenta. In this study, we clarified that expression of the system A molecule can be more quickly increased in response to the osmotic stress than other molecules and we investigated how the system A molecules is induced by hypertonic stress.

Research Products

• [Journal Article] Hypotaurine is a substrate of GABA transporter family members GAT2/Slc6a13 and TAUT/Slc6a6. (2018)
  • Author(s): Nishimura T, Higuchi K, Yoshida Y, Sugita-Fujisawa Yuki, Kojima K, Sugimoto M, Santo M, Tomi M, Nakashima E.
  • Journal Title: Biol Pharm Bull. Volume: in press
  • NAID: 130007491801
  • Peer Reviewed
• [Journal Article] Co-localization of microsomal prostaglandin E synthase-1 with cyclooxygenase-1 in layer II of murine placental syncytiotrophoblasts (2017)
  • Author(s): M. Inagaki, T. Nishimura, S. Akanuma, T. Nakanishi, M. Tachikawa, I. Tamai, K. Hosoya, E. Nakashima, M. Tomi
  • Journal Title: Placenta Volume: 53 Pages: 76-82
  • DOI: 10.1016/j.placenta.2017.04.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cellular uptake of levocetirizine by Organic Anion Transporter 4 (2017)
  • Author(s): Noguchi S, Nishimura T, Mukaida S, Benet LZ, Nakashima E, Tomi M
  • Journal Title: Journal of Pharmaceutical Sciences Volume: 印刷中 Issue: 9 Pages: 2895-2898
  • DOI: 10.1016/j.xphs.2017.03.026
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Layer II of placental syncytiotrophoblasts expresses MDR1 and BCRP at the apical membrane in rodents (2016)
  • Author(s): T. Akashi, T. Nishimura, Y. Takaki, M. Takahashi, B.C. Shin, M. Tomi, E. Nakashima
  • Journal Title: Reprod. Toxicol. Volume: 65 Pages: 375-381
  • DOI: 10.1016/j.reprotox.2016.09.002
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Role of OAT4 in uptake of estriol precursor 16α-hydroxy dehydroepiandrosterone sulfate into human placental syncytiotrophoblasts from fetus. (2015)
  • Author(s): Tomi M, Eguchi H, Ozaki M, Tawara T, Nishimura S, Higuchi K, Maruyama T, Nishimura T, Nakashima E.
  • Journal Title: Endocrinol Volume: 156 Issue: 7 Pages: 2704-2712
  • DOI: 10.1210/en.2015-1130
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Organic anion transporter 4-mediated transport of olmesartan at basal plasma membrane of human placental barrier (2015)
  • Author(s): Noguchi S, Nishimura T, Fujibayashi A, Maruyama T, Tomi M, Nakashima E.
  • Journal Title: J Pharm Sci Volume: 104 Issue: 9 Pages: 3128-3135
  • DOI: 10.1002/jps.24434
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Protective effect of hypotaurine against oxidative stress-induced cytotoxicity in rat placental trophoblasts (2015)
  • Author(s): Nishimura T, Duereh M, Sugita Y, Yoshida Y, Higuchi K, Tomi M, Nakashima E.
  • Journal Title: Placenta Volume: 36 Issue: 6 Pages: 693-698
  • DOI: 10.1016/j.placenta.2015.02.014
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 浸透圧誘導性SNAT2発現に関与する3’非翻訳領域の同定 (2017)
  • Author(s): 吉田 啓佑、西村 友宏、野口 幸希、中島 恵美、登美 斉俊
  • Organizer: 第61回日本薬学会関東支部会
• [Presentation] Induction Mechanism of Sodium-dependent Amino Acid Transporter2(SNAT2)in Rat Placental Trophoblasts (2016)
  • Author(s): Tomohiro Nishimura, Emi Nakashima, Masatoshi Tomi
  • Organizer: The 1st workshop for Japan-Korea Young Scientists on Pharmaceutics
  • Place of Presentation: Kyoto Kyoiku Bunka Center (Kyoto, Kyoto)
  • Year and Date: 2016-06-24
  • Int'l Joint Research
• [Presentation] Acute Induction of sodium-dependent neutral amino acid transporter 2 (SNAT2) expression by hyperosmotic condition in placental syncytiotrophoblasts (2016)
  • Author(s): Tomohiro Nishimura, Keisuke Yoshida, Yu Takahashi, Masatoshi Tomi, Emi Nakashima
  • Organizer: 11th International ISSX Meeging
  • Place of Presentation: Busan Convention and Exhibition Center (Korea, Busan)
  • Year and Date: 2016-06-12
  • Int'l Joint Research
• [Presentation] Induction of sodium-dependent neutral amino acid transporter 2 (SNAT2) by hypertonic stress in placental syncytiotrophoblasts (2015)
  • Author(s): Nishimura T, Kojima T, Takahashi Y, Tomi M, Nakashima E.
  • Organizer: Asian Federation for Pharmaceutical Sciences 2015
  • Place of Presentation: Bangkok (Thailand)
  • Year and Date: 2015-11-25
  • Int'l Joint Research
• [Presentation] 胎盤trophoblast におけるSNAT2 の高浸透圧刺激による急速発現調節 (2015)
  • Author(s): 西村友宏、小澤夏美、高橋優、登美斉俊、中島恵美
  • Organizer: 日本薬剤学会第30年会
  • Place of Presentation: 長崎ブリックホール（長崎県・長崎市）
  • Year and Date: 2015-05-21