Functional roles of arginine methylation on vascular networks for nutritional supply

• Project/Area Number: 25252062
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied molecular and cellular biology
• Research Institution: University of Tsukuba
• Principal Investigator: FUKAMIZU Akiyoshi 筑波大学, 生命領域学際研究センター, 教授 (60199172)
• Co-Investigator(Renkei-kenkyūsha): ISHIDA Junji 筑波大学, 生命領域学際研究センター, 講師 (30323257) ; KAKO Koichiro 筑波大学, 生命環境系, 講師 (60311594) ; KIM Jun-Dal 筑波大学, 生命領域学際研究センター, 講師 (90570036) ; SUGIYAMA Fumihiro 筑波大学, 医学医療系, 教授 (90226481) ; KASUYA Yoshitoshi 千葉大学, 医学系研究科, 准教授 (70221877)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥46,150,000 (Direct Cost: ¥35,500,000、Indirect Cost: ¥10,650,000); Fiscal Year 2016: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000); Fiscal Year 2015: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000); Fiscal Year 2014: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000); Fiscal Year 2013: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
• Keywords: 栄養 / 血管 / PRMT1 / 内皮細胞特異的ノックアウトマウス / イメージング / 透明化 / 二光子顕微鏡 / 代謝 / 血管内皮細胞 / ノックアウトマウス / 栄養補給路 / アルギニンメチル化酵素 / 内皮細胞

Outline of Final Research Achievements

Angiogenesis is important in embryonic development, and endothelial cells play a critical role in these processes. Protein arginine methyltransferase 1 (PRMT1) is involved in multiple cellular functions including proliferation and differentiation, and is expressed in vascular endothelial cells, which are responsible for angiogenesis during embryonic development. Since homozygous mutation of the Prmt1 gene results in early embryonic lethality in mice, little has been known about its physiological importance. In the present study, we found that the endothelial cell-specific PRMT1 deficient mice (PRMT1-ECKO) died within embryonic day 15. Macroscopic observation showed that the temporal arteries were poorly perfused with blood as compared with controls. Whole mount in vivo 3D imaging revealed the dilated and segmentalized luminal structures in PRMT1-ECKO fetuses. Our findings clearly provide evidence that PRMT1 is essential for normal vascular formation during embryogenesis.

Research Products

• [Journal Article] Angiodysplasia in embryo lacking protein arginine methyltransferase 1 (PRMT1) in vascular endothelial cells. (2017)
  • Author(s): Ishimaru, T., Ishida, J., Kim, JD., Mizukami, H., Hara, K., Hashimoto, M., Yagami, KI., Sugiyama, F., and Fukamizu, A.
  • Journal Title: Journal of Biochemistry Volume: 161 Pages: 255-258
  • DOI: 10.1093/jb/mvw095
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Severe hypomyelination and developmental defects are caused in mice lacking protein arginine methyltransferase 1 (PRMT1) in the central nervous system. (2016)
  • Author(s): Hashimoto, M., Murata, M., Ishida, J., Kanou, A., Kasuya, Y., and Fukamizu, A.
  • Journal Title: J. Biol. Chem. Volume: 291 Issue: 5 Pages: 2237-2245
  • DOI: 10.1074/jbc.m115.684514
  • NAID: 120007128484
  • Peer Reviewed / Open Access
• [Journal Article] Novel helical assembly in arginine methyltransferase 8 (2016)
  • Author(s): Toma-Fukai S, Kim JD, Park KE, Kuwabara N, Shimizu N, Krayukhina E, Uchiyama S, Fukamizu A, Shimizu T
  • Journal Title: Journal of Molecular Biology Volume: 428 Issue: 6 Pages: 1197-1208
  • DOI: 10.1016/j.jmb.2016.02.007
  • Peer Reviewed / Open Access
• [Journal Article] PRMT8 as a phospholipase regulates Purkinje cell dendritic arborization and motor coordination. (2015)
  • Author(s): Kim, J.D., Park, K.E., Ishida, J., Kako, K., Hamada, J., Kani, S., Takeuchi, M., Namiki, K., Fukui, H., Fukuhara, S., Hibi, M,. Kobayashi, M., Kanaho, Y., Kasuya, Y., Mochizuki, N., Fukamizu, A.
  • Journal Title: Sci. Adv. Volume: 1 Issue: 11
  • DOI: 10.1126/sciadv.1500615
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Erythropoiesis and Blood Pressure Are Regulated via AT1 Receptor by Distinctive Pathways (2015)
  • Author(s): Kato H, Ishida J, Matsusaka T, Ishimaru T, Tanimoto K, Sugiyama F, Yagami K, Nangaku M, Fukamizu A
  • Journal Title: PLoS One Volume: 10 Issue: 6 Pages: e0129484-e0129484
  • DOI: 10.1371/journal.pone.0129484
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A mouse renin distal enhancer is essential for blood pressure homeostasis in BAC-rescued renin-null mutant mice. (2014)
  • Author(s): Tanimoto K, Kanafusa S, Ushiki A, Matsuzaki H, Ishida J, Sugiyama F, Fukamizu A
  • Journal Title: J. Recept. Signal Transduct. Volume: 34 Issue: 5 Pages: 401-409
  • DOI: 10.3109/10799893.2014.908917
  • Peer Reviewed
• [Journal Article] Protein arginine methyltransferase 7 has a novel homodimer-like structure formed by tandem repeats (2014)
  • Author(s): Hasegawa, M., Toma-Fukai, S., Kim, JD., Fukamizu, A., and Shimizu, T.
  • Journal Title: FEBS Letter Volume: 588 Issue: 10 Pages: 1942-1948
  • DOI: 10.1016/j.febslet.2014.03.053
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Detection of choline and phosphatidic acid (PA) catalyzed by Phospholipase D (PLD) using MALDI-QIT-TOF/MS with 9-aminoacridine matrix (2014)
  • Author(s): Park KE, Kim JD, Nagashima Y, Kako K, Daitoku H, Matsui M, Park GG, Fukamizu A
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: 78 Issue: 6 Pages: 981-988
  • DOI: 10.1080/09168451.2014.910102
  • Peer Reviewed
• [Journal Article] p38 mitogen-activated protein kinase accelerates emphysema in mouse model of chronic obstructive pulmonary disease. (2014)
  • Author(s): Amano H, Murata K, Matsunaga H, Tanaka K, Yoshioka K, Kobayashi T, Ishida J, Fukamizu A, Sugiyama F, Sudo T, Kimura S, Tatsumi K, Kasuya Y.
  • Journal Title: J Recept Signal Transduc Volume: in press Issue: 4 Pages: 299-306
  • DOI: 10.3109/10799893.2014.896380
  • Peer Reviewed
• [Journal Article] Truncated Cables1 causes agenesis of the corpus callosum in mice (2014)
  • Author(s): Mizuno S, Dinh T, Mizobuchi A, Iseki H, Mizuno-Iijima S, Kim J-D, Ishida J, Matsuda Y, Kunita S, Fukamizu A, Yagami K, Sugiyama F
  • Journal Title: Laboratory Investigation Volume: 94 Issue: 3 Pages: 321-330
  • DOI: 10.1038/labinvest.2013.146
  • Peer Reviewed
• [Journal Article] Lung surfactant levels are regulated by Ig-Hepta/GPR116 by monitoring surfactant protein D (2013)
  • Author(s): Fukuzawa, T., Ishida, J
  • Journal Title: PLoS One Volume: 8 Issue: 7 Pages: e69451-e69451
  • DOI: 10.1371/journal.pone.0069451
  • Peer Reviewed
• [Journal Article] Apelin is a positive regulator of ACE2 in failing hearts. (2013)
  • Author(s): Sato T, Suzuki T, Watanabe H, K adowaki A, Fukamizu A, Liu PP, Kimura A, Ito H, Penninger JM, I mai Y, Kuba K.
  • Journal Title: J Clin Invest Volume: 123 Issue: 12 Pages: 5203-11
  • DOI: 10.1172/jci69608
  • Peer Reviewed
• [Presentation] タンパク質はmultilingual? (2017)
  • Author(s): 深水 昭吉
  • Organizer: 生命の機能とかたち 連携セミナー
  • Place of Presentation: 筑波大学総合研究棟A棟（茨城県 つくば市）
  • Year and Date: 2017-03-06
  • Invited
• [Presentation] アルギニンメチル化酵素の役割とその多様性 (2016)
  • Author(s): 深水 昭吉
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県 横浜市）
  • Year and Date: 2016-12-01
  • Invited
• [Presentation] 心血管系に作用するアルギニンメチル化の機能と多様性 (2016)
  • Author(s): 深水 昭吉
  • Organizer: シグナル伝達医学講演会
  • Place of Presentation: 神戸大学医学部臨床研究棟（兵庫県 神戸市）
  • Year and Date: 2016-11-24
  • Invited
• [Presentation] エネルギー代謝と転写制御 (2016)
  • Author(s): 深水 昭吉
  • Organizer: 第11回 臨床ストレス応答学会大会
  • Place of Presentation: 山口大学医学部霜仁会館（山口県 宇部市）
  • Year and Date: 2016-11-11
  • Invited
• [Presentation] Arginine methylation:its functional roles and diversity (2016)
  • Author(s): Akiyoshi Fukamizu
  • Organizer: Pharmacology Seminar
  • Place of Presentation: Pennstate Hershey College of Medecine, Pennsylvania (U. S. A.）
  • Year and Date: 2016-10-20
  • Int'l Joint Research / Invited
• [Presentation] Arginine methylation and its conditional roles in vivo: PRMT1 and PRMT8 (2016)
  • Author(s): Akiyoshi Fukamizu
  • Organizer: Asian Epigenomics Meeting 2016
  • Place of Presentation: AMRL Conference Hall, Bangalore (India)
  • Year and Date: 2016-09-30
  • Int'l Joint Research / Invited
• [Presentation] TCAサイクルとアセチル化・脱アセチル化による初期発生の調節 (2016)
  • Author(s): 深水 昭吉
  • Organizer: 第89回 日本生化学会大会
  • Place of Presentation: 仙台国際センター（宮城県 仙台市）
  • Year and Date: 2016-09-26
  • Invited
• [Presentation] 線虫飢餓モデル・妊娠高血圧症モデル (2016)
  • Author(s): 深水 昭吉
  • Organizer: 第5回 日本DOHaD研究会学術集会
  • Place of Presentation: 国立成育医療研究センター（東京都 世田谷区）
  • Year and Date: 2016-07-24
  • Invited
• [Presentation] 寿命を動かす代謝の仕組み (2016)
  • Author(s): 深水 昭吉
  • Organizer: 第39回 日本基礎老化学会大会
  • Place of Presentation: 伊勢原市民文化会館（神奈川県 伊勢原市）
  • Year and Date: 2016-05-27
  • Invited
• [Presentation] アルギニンメチル基転移酵素 PRMT1 による心機能制御機構の解明 (2015)
  • Author(s): 村田知弥、陸偉哲、橋本美涼、石田純治、深水昭吉
  • Organizer: 第19回 日本心血管内分泌代謝学
  • Place of Presentation: 神戸国際会議場、兵庫県神戸市
  • Year and Date: 2015-12-11
• [Presentation] 血管内皮タンパク質アルギニンメチル基転移酵素・PRMT1の機能解析 (2015)
  • Author(s): 石丸友博、石田純治、金 俊達、仲島由佳、橋本美涼、水上早瀬、杉山文博、八神健一、深水昭吉
  • Organizer: 第19回 日本心血管内分泌代謝学
  • Place of Presentation: 神戸国際会議場、兵庫県神戸市
  • Year and Date: 2015-12-11
• [Presentation] 血管内皮におけるタンパク質アルギニンメチル基転移酵素・PRMT1の機能解析 (2015)
  • Author(s): 石丸友博、石田純治、金 俊達、仲島由佳、橋本美涼、水上早瀬、杉山文博、八神健一、深水昭吉
  • Organizer: 第51回高血圧関連疾患モデル学会
  • Place of Presentation: 千里ライフサイエンスセンター、大阪府豊中市
  • Year and Date: 2015-10-31
• [Presentation] 妊娠高血圧モデルマウスにおいて増加するアミノプロダクトの同定 (2014)
  • Author(s): 加香孝一郎，中村あゆみ，川崎祥平，永島裕介，石田純治，深水昭吉
  • Organizer: 第18回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 横浜, 横浜市開港記念館
  • Year and Date: 2014-11-21
• [Presentation] 妊娠高血圧マウスに対する複数の降圧剤投与による病態改善効果 (2014)
  • Author(s): 石丸友博，石田純治，中村匠子、橋本美涼，松倉頼，Baasanjav Altansarnai，Haojun Xu，水上早瀬，権哲源，杉山文博，八神健一，深水昭吉
  • Organizer: 第5回 Molecular cardiovascular conference II
  • Place of Presentation: 神戸, 神戸ベイシェラトンホテル
  • Year and Date: 2014-09-05
• [Presentation] Ameliorative effect of L-type calcium channel blocker on the pathological conditions in mice with pregnancy-associated hypertension (2014)
  • Author(s): Haojun Xu, Junji Ishida, Tomohiro Ishimaru, Altansarnai Baasanjav, Misuzu Hashimoto, Kazuyuki Noguchi, and Akiyoshi Fukamizu
  • Organizer: 第5回 Molecular cardiovascular conference II
  • Place of Presentation: 神戸, 神戸ベイシェラトンホテル
  • Year and Date: 2014-09-05
• [Presentation] Dietary methionine restriction in axenic medium decreases both methionine and S-adenosyl-L-methionine levels (2014)
  • Author(s): Yamauchi, R., Hirota, K., Xu, Z., Iizuka, K., Daitoku, H., Kako, K., Fukamizu, A.
  • Organizer: 6th Asia-pacific C.elegans Meeting
  • Place of Presentation: 奈良, 奈良県新公会堂
  • Year and Date: 2014-07-15
• [Presentation] 妊娠高血圧症候群病態に関与するアミノプロダクトの探索と同定 (2014)
  • Author(s): 加香孝一郎、永島裕介，石田純治，土屋敬広，嶋田崇史，深水昭吉
  • Organizer: 第9回年会日本ケミカルバイオロジー学会
  • Place of Presentation: 大阪府, 大阪大学豊中キャンパス
  • Year and Date: 2014-06-19
• [Presentation] Combinatorial treatment with antihypertensive drugs prevents HELLP syndrome exacerbated by endothelial dysfunction in pregnant hypertensive mice. (2014)
  • Author(s): Junji Ishida, Tomohiro Ishimaru, Tanomu Matsukura, Shoko Nakamura, Haojun Xu, Altansarnai Baasanjav, Misuzu Hashimoto, Kazuya Murata, Katsumasa Nagano, Fumihiro Sugiyama, Ken-ichi Yagami, and Akiyoshi Fukamizu
  • Organizer: 第18回 国際血管生物学会
  • Place of Presentation: 京都府, みやこめっせ
  • Year and Date: 2014-04-14
• [Presentation] Vascular endothelial dysfunction in mice with pregnancy-associated hypertension (2014)
  • Author(s): Tomohiro Ishimaru, Junji Ishida, Tanomu Matsukura, Katsumasa Nagano, Fumihiro Sugiyama, Ken-ichi Yagami, and Akiyoshi Fukamizu
  • Organizer: 第18回 国際血管生物学会
  • Place of Presentation: 京都府, みやこめっせ
  • Year and Date: 2014-04-14