Laboratory Medicine of Lysophospholipids

• Project/Area Number: 25253040
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: The University of Tokyo
• Principal Investigator: Yatomi Yutaka 東京大学, 医学部附属病院, 教授 (60200523)
• Research Collaborator: KURANO Makoto 東京大学, 医学部附属病院, 助教 (60621745) ; IKEDA Hitoshi 東京大学, 医学部附属病院, 准教授 (80202422)
• Project Period (FY): 2013-10-21 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥33,020,000 (Direct Cost: ¥25,400,000、Indirect Cost: ¥7,620,000); Fiscal Year 2015: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000); Fiscal Year 2014: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000); Fiscal Year 2013: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
• Keywords: 臨床検査医学 / リゾリン脂質 / リゾホスファチジン酸 / スフィンゴシン1-リン酸 / リゾホスファチジルセリン / オートタキシン / アポリポタンパク質M / ホスファチジルセリン特異的ホスホリパーゼA1 / アポタンパク質M / リゾホスファチジン差 / 生理活性脂質 / 臨床検査

Outline of Final Research Achievements

It is established that lysophospholipids constitute a new family of lipid mediators and are involved in a broad range of (patho)physiological actions. We have examined the involvement of lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P), and lysophosphatidylserine (LysoPS) in human diseases and pursued the clinical introduction of the measurement of these lysophospholipids and their related proteins; LPA, S1P, LysoPS are the most well characterized lysophospholipids. Autotaxin (ATX) reflects the LPA level in vivo, and ATX assay kit is promising as an IVD kit. Furthermore, the minor apolipoprotein ApoM is the carrier of S1P and can be a surrogate marker of S1P while phosphatidylserine-specific phospholipase A1 (PS-PLA1), which produces LysoPS, can be a biomarker reflecting the in vivo action of LysoPS. We have succeeded in the establishment of the assay systems not only for ATX but also for ApoM and PS-PLA1, and revealed the clinical importance of their measurements.

Research Products

• [Journal Article] Increased mRNA Levels of Sphingosine Kinases and S1P Lyase and Reduced Levels of S1P Were Observed in Hepatocellular Carcinoma in Association with Poorer Differentiation and Earlier Recurrence. (2016)
  • Author(s): Uranbileg B, Ikeda H, Kurano M, Enooku K, Sato M, Saigusa D, Aoki J, Ishizawa T, Hasegawa K, Kokudo N, Yatomi Y.
  • Journal Title: PLoS One Volume: 11 Issue: 2 Pages: e0149462-e0149462
  • DOI: 10.1371/journal.pone.0149462
  • Peer Reviewed / Open Access
• [Journal Article] Serum Autotaxin Levels Are Associated with Proteinuria and Kidney Lesions in Japanese Type 2 Diabetic Patients with Biopsy-proven Diabetic Nephropathy (2016)
  • Author(s): Shimizu M, Furuichi K, Toyama T, Yamahana J, Ohkawa R, Igarashi K, Aoki J, Kaneko S, Yatomi Y, Wada T
  • Journal Title: Internal Medicine Volume: 55 Issue: 3 Pages: 215-221
  • DOI: 10.2169/internalmedicine.55.5473
  • NAID: 130005122604
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Resveratrol exerts a biphasic effect on apolipoprotein M. (2016)
  • Author(s): Kurano M, Hara M, Nojiri T, Ikeda H, Tsukamoto K, Yatomi Y.
  • Journal Title: Br J Pharmacol Volume: 173 Issue: 1 Pages: 222-233
  • DOI: 10.1111/bph.13360
  • Peer Reviewed / Open Access
• [Journal Article] Blood levels of serotonin are specifically correlated with plasma lysophosphatidylserine among the glycero-lysophospholipids (2015)
  • Author(s): Kurano M, Dohi T, Nojiri T, Kobayashi T, Hirowatari Y, Inoue A, Kano K, Matsumoto H, Igarashi K, Nishikawa M, Miyauchi K, Daida H, Ikeda H, Aoki J, Yatomi Y
  • Journal Title: BBA Clin Volume: 4 Pages: 92-98
  • DOI: 10.1016/j.bbacli.2015.08.003
  • Peer Reviewed / Open Access
• [Journal Article] Placental autotaxin expression is diminished in women with pre-eclampsia (2015)
  • Author(s): Ichikawa M, Nagamatsu T, Schust DJ, Kawai-Iwasawa Y, Kawana K, Yamashita T, Osuga Y, Aoki J, Yatomi Y, Fujii T
  • Journal Title: J Obstet Gynaecol Res Volume: 41 Issue: 9 Pages: 1406-11
  • DOI: 10.1111/jog.12742
  • Peer Reviewed
• [Journal Article] A New Enzyme Immunoassay for the Quantitative Determination of Classical Autotaxins (ATXα, ATXβ, and ATXγ) and Novel Autotaxins (ATXδ and ATXε) (2015)
  • Author(s): Tokuhara Y, Kurano M, Shimamoto S, Igarashi K, Nojiri T, Kobayashi T, Masuda A, Ikeda H, Nagamatsu T, Fujii T, Aoki J, Yatomi Y
  • Journal Title: PLoS One Volume: 10 Issue: 6 Pages: e0130074-e0130074
  • DOI: 10.1371/journal.pone.0130074
  • Peer Reviewed / Open Access
• [Journal Article] Possible involvement of sphingomyelin in the regulation of the plasma sphingosine 1-phosphate level in human subjects (2015)
  • Author(s): Ohkawa R, Kurano M, Mishima Y, Nojiri T, Tokuhara Y, Kishimoto T, Nakamura K, Okubo S, Hosogaya S, Ozaki Y, Yokota H, Igarashi K, Ikeda H, Tozuka M, Yatomi Y
  • Journal Title: Clinical Biochemistry Volume: 48 Issue: 10-11 Pages: 690-697
  • DOI: 10.1016/j.clinbiochem.2015.03.019
  • Peer Reviewed
• [Journal Article] LDL Receptor and ApoE are Involved in the Clearance of ApoM-associated Sphingosine 1-phosphate (2015)
  • Author(s): Kurano M, Tsukamoto K, Hara M, Ohkawa R, Ikeda H, Yatomi Y.
  • Journal Title: J Biol Chem Volume: 290 Issue: 4 Pages: 2477-88
  • DOI: 10.1074/jbc.m114.596445
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Lysophosphatidylserine has Bilateral Effects on Macrophages in the Pathogenesis of Atherosclerosis (2015)
  • Author(s): Nishikawa M, Kurano M, Ikeda H, Aoki J, Yatomi Y
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 22 Issue: 5 Pages: 518-526
  • DOI: 10.5551/jat.25650
  • NAID: 130004704381
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed / Open Access
• [Journal Article] Lysophosphatidylserine has Bilateral Effects on Macrophages in the Pathogenesis of Atherosclerosis (2015)
  • Author(s): Nishikawa M, Kurano M, Ikeda H, Aoki J, Yatomi Y
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 22
  • NAID: 130004704381
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Possible involvement of minor lysophospholipids in the increase in plasma lysophosphatidic acid in acute coronary syndrome. (2015)
  • Author(s): Kurano M, Suzuki A, Inoue A, Tokuhara Y, Kano K, Matsumoto H, Igarashi K, Ohkawa R, Nakamura K, Dohi T, Miyauchi K, Daida H, Tsukamoto K, Ikeda H, Aoki J, Yatomi Y
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 35 Issue: 2 Pages: 463-470
  • DOI: 10.1161/atvbaha.114.304748
  • Peer Reviewed / Open Access
• [Journal Article] Lysophosphatidylserine stimulates chemotactic migration of colorectal cancer cells through GPR34 and PI3K/Akt pathway (2014)
  • Author(s): Iida, Y. H. Tsuno N Kishikawa, J. Kaneko, K. Murono, K. Kawai, K. Ikeda, T. Ishihara, S. Yamaguchi, H. Sunami, E. Kitayama, J. Yatomi, Y. Watanabe, T.
  • Journal Title: Anticancer Res Volume: 34 Pages: 5465-72
  • Peer Reviewed
• [Journal Article] Platelet-derived sphingosine 1-phosphate induces migration of Jurkat T cells (2014)
  • Author(s): Iino J, Osada M, Kurano M, Kaneko M, Ohkawa R, Satoh Y, Okubo S, Ozaki Y, Tozuka M, Tsuno NH, Yatomi Y
  • Journal Title: Lipids Health Dis Volume: 13 Issue: 1 Pages: 150-150
  • DOI: 10.1186/1476-511x-13-150
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Induction of insulin secretion by apolipoprotein M, a carrier for sphingosine 1-phosphate. (2014)
  • Author(s): Kurano M, Hara M, Tsuneyama K, Sakoda H, Shimizu T, Tsukamoto K, Ikeda H, Yatomi Y.
  • Journal Title: Biochim Biophys Acta. Volume: 1841 Issue: 9 Pages: 1217-1226
  • DOI: 10.1016/j.bbalip.2014.05.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Modulation of sphingosine-1-phosphate and apolipoprotein M levels in the plasma, liver and kidneys in streptozotocin-induced diabetic mice (2014)
  • Author(s): Nojiri T, Kurano M, Tokuhara Y, Ohkubo S, Hara M, Ikeda H, Tsukamoto K, Yatomi Y
  • Journal Title: J Diabetes Investig Volume: 5 Issue: 6 Pages: 639-48
  • DOI: 10.1111/jdi.12232
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ENPP2 contributes to adipose tissue expansion and insulin resistance in diet-induced obesity. (2014)
  • Author(s): Nishimura S, Nagasaki M, Okudaira S, Aoki J, Ohmori T, Ohkawa R, Nakamura K, Igarashi K, Yamashita H, Eto K, Uno K, Hayashi N, Kadowaki T, Komuro I, Yatomi Y, Nagai R.
  • Journal Title: Diabetes Volume: 63 Issue: 12 Pages: 4154-4164
  • DOI: 10.2337/db13-1694
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Increased serum autotaxin levels in hepatocellular carcinoma patients were caused by background liver fibrosis but not by carcinoma (2014)
  • Author(s): Kondo M, Ishizawa T, Enooku K, Tokuhara Y, Ohkawa R, Uranbileg B, Nakagawa H, Tateishi R, Yoshida H, Kokudo N, Koike K, Yatomi Y, Ikeda H
  • Journal Title: Clin Chim Acta Volume: 433C Pages: 128-134
  • DOI: 10.1016/j.cca.2014.03.006
  • Peer Reviewed
• [Journal Article] Liver involvement in sphingosine 1-phosphate dynamism revealed by adenoviral hepatic overexpression of apolipoprotein M (2013)
  • Author(s): Kurano, M., Tsukamoto, K., Ohkawa, R., Hara, M., Iino, J., Kageyama, Y., Ikeda, H., and Yatomi, Y.
  • Journal Title: Atherosclerosis Volume: 229 Issue: 1 Pages: 102-109
  • DOI: 10.1016/j.atherosclerosis.2013.04.024
  • Peer Reviewed
• [Journal Article] Sphingosine 1-phosphate release from platelets during clot formation: close correlation between platelet count and serum sphingosine 1-phosphate concentration (2013)
  • Author(s): Ono Y
  • Journal Title: Lipids Health Dis Volume: 12 Issue: 1 Pages: 20-20
  • DOI: 10.1186/1476-511x-12-20
  • Peer Reviewed
• [Presentation] 生理活性脂質の臨床化学 (2014)
  • Author(s): 矢冨 裕
  • Organizer: 第54回日本臨床化学会年次学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-09-05 – 2014-09-07
  • Invited
• [Remarks] 東京大学医学部附属病院検査部
  • URL: http://lab-tky.umin.jp/index.html
• [Remarks] 東京大学医学部附属病院検査部
  • URL: http://lab-tky.umin.jp