Inhibition of angiogenesis through a targeting miRNA

2010 Fiscal Year Final Research Report

• Project/Area Number: 20592063
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kanazawa Medical University
• Principal Investigator: YOSHITAKE Yoshino Kanazawa Medical University, 医学部, 准教授 (00150764)
• Co-Investigator(Kenkyū-buntansha): YONEKURA Hidoto 金沢医科大学, 医学部, 教授 (80240373) ; YAGUCHI Hiromoto 金沢医科大学, 医学部, 助教 (40410344)
• Project Period (FY): 2008 – 2010
• Keywords: 血管内皮細胞 / miRNA / 増殖性網膜症 / sFlt-1 / レンチウイルス / 白内障 / UVB / 水晶体上皮細胞

Research Abstract

When human microvascular endothelial cells (HMVEC), a constituent of microvessels wherein angiogenesis occurs in diseases, formed the capillary like tubes on plastic plate, we found the expression of some specific genes and micro RNA (small non-coding RNA). Hypoxia (2.5%O_2 ) down-regulated anti-angiogenic factor, sFlt-1 while it up-regulated angiogenic factor, VEGF in HMVEC. UV exposure to human lens epithelial cells stimulated the secretion of several cytokines, which may result in cataract. Our research might be useful for diminishing the actions of causing-disease genes.

Research Products

• [Journal Article] An intracellular amyloid-R toxicity is counteracted by expressionofHomerlain neocortex pyramidal cells. (2011)
  • Author(s): Yamamoto K, Ueta Y, Yamamoto R, Inoue N, Inokuchi K, Yonekura H, Kato N
  • Journal Title: J.Neurosci. (in press)
  • Peer Reviewed
• [Journal Article] Hypoxia down-regulates sFlt-1 (sVEGFR-1) expression in human microvascular endothelial cells by a mechanism involving mRNA alternative processing. (2011)
  • Author(s): Ikeda T, Sun L, Tsuruoka N, Ishigaki Y, Yoshitomi Y, Yoshitake Y, Yonekura H
  • Journal Title: Biochem.J. 436 Pages: 399-407
  • Peer Reviewed
• [Journal Article] Septic shock is associated with receptor for advanced glycation endproducts (RAGE) ligation of LPS. (2011)
  • Author(s): Yamamoto Y, Harashima A, Saito H, Tsuneyama K, Munesue S, Motoyoshi S, Han D, Watanabe T, Asano M, Takasawa S, Okamoto H, Shimura S, Karasawa T, Yonekura H, Yamamoto H
  • Journal Title: J.Immunol. 186 Pages: 3248-57
  • Peer Reviewed
• [Journal Article] Identification of the COL2Al Mutation in Patients with Type I Stickler Syndrome Using RNA from Freshly Isolated Peripheral White Blood Cells. (2011)
  • Author(s): Yaguchi H, Ikeda T, Osada H, Yoshitake Y, Sasaki H, Yonekura H
  • Journal Title: Genet.Test.Mol.Biomarkers. 15 Pages: 231-237
  • Peer Reviewed
• [Journal Article] ピアルロン酸ナトリウム点眼液の角膜細胞に対する影響の検討 (2011)
  • Author(s): 福田正道、矢口裕基、藤田信之、稲垣伸亮、長田ひろみ、柴田奈央子、佐々木洋
  • Journal Title: 新しい眼科 28 Pages: 549-552
• [Journal Article] Ultraviolet B-induced expression of amphiregulin and growth differentiation factor 15 in human lens epithelial cells. (2011)
  • Author(s): Yoshitake Y, Osada H,, Ikeda T, Ishigaki Y, Takata T, Tomosugi N, Sasaki H, Yonekura H
  • Journal Title: Mol.Vis. 17 Pages: 159-169
  • Peer Reviewed
• [Journal Article] Cyclin-dependent kinase inhibitor p16 and p21 expression, and cell cycle change in human Lens epithelial cell line SRA01/04 following contact inhibition in normal culture. (2011)
  • Author(s): Yamashiro Y, Sasaki H, Ibaraki N, Nagai K, Kawakami Y, Yaguchi H, Fujita N, Osada H, Sasaki K
  • Journal Title: Ophtal.Res. 46 Pages: 38-43
  • Peer Reviewed
• [Journal Article] Regulation ofalternative splicing of the receptor for advanced glycation endproducts (RAGE) through G-rich cis-elements and heterogenous nuclear ribonucleoprotein (hnRNP) H. (2010)
  • Author(s): Ohe K, Watanabe T, Harada SI, Munesue S, Yamamoto Y, Yonekura H, Yamamoto H
  • Journal Title: J.Biochem. 147 Pages: 651-659
  • Peer Reviewed
• [Journal Article] Identification of HITS, anewly identified TU3A/DDR1 family of protein(FAM107B), in cancer cells by heat shock stimulation. (2010)
  • Author(s): Nakajima H, Ishigaki Y, Xia Q, Ikeda T, Yoshitake Y, Yonekura H, Nojima T, Tanaka T, Umehara H, Tomosugi N, Takada T, Shimasaki T, Nakaya N, Sato I, Koizumi K, Kawakami K, Minamoto T, Motoo Y
  • Journal Title: Int.J.Oncol. 37 Pages: 583-593
  • Peer Reviewed
• [Journal Article] Solution structure ofthe variable-type domain of the receptor for advanced glycation end products : new insight into AGE-RAGE interachon. (2008)
  • Author(s): Matsumoto S, Yoshida T, Murata H, Harada S, Fujita N, Nakamura S, Yamamoto Y, Watanabe T, Yonekura H, Yamamoto H, Ohkubo T, Kobayashi Y
  • Journal Title: Biochemistry 47 Pages: 12299-12311
  • Peer Reviewed
• [Presentation] Soluble VEGFR-1 production is down-regulated under hypoxia in human microvascular endothelial cells by a mechanism involving alternative mRNA 3'-end processing. (2011)
  • Author(s): Ikeda T, Yoshitomi Y, Ishigaki Y, Yoshitake Y, Yonekura H
  • Organizer: 日本分子生物学会第11回春季シンポジウム・金沢国際がん生物学シンポジウム
  • Place of Presentation: 石川県立音楽堂(金沢市)
  • Year and Date: 20110525-20110526
• [Presentation] 低酸素刺激による微小血管内皮細胞の可溶型VEGF受容体(可溶型Flt-1)産生の抑制 (2011)
  • Author(s): 池田崇之、吉冨泰夫、石垣靖人、吉竹佳の、米倉秀人
  • Organizer: 第83回日本生化学会北陸支部会
  • Place of Presentation: 金沢大学角間キャンパス(金沢市)
  • Year and Date: 2011-05-28
• [Presentation] UVB曝露ストレスによる水晶体上皮細胞のAmphiregulin発現の上昇 (2010)
  • Author(s): 吉竹佳の、長田ひろみ、池田崇之、石垣靖人、高田尊信、友杉直久、佐々木洋、米倉秀人
  • Organizer: 第83回日本生化学会大会・第33回日本分子生物学会年会・合同大会
  • Place of Presentation: 神戸ポートアイランド(神戸市)
  • Year and Date: 20101207-20101210
• [Presentation] 低酸素状態は3'端プロセシングを制御することによって血管内皮細胞での可溶型VEGF受容体(可溶型Flt-1)産生を減少させる (2010)
  • Author(s): 池田崇之、吉竹佳の、米倉秀人
  • Organizer: 第83回日本生化学会大会・第33回日本分子生物学会年会・合同大会
  • Place of Presentation: 神戸ポートアイランド(神戸市)
  • Year and Date: 20101207-20101210
• [Presentation] 可溶型VEGF受容体(可溶型Flt-1)産生を制御する選択的3'端プロセシングメカニズムの解明 (2010)
  • Author(s): 池田崇之、吉竹佳の、米倉秀人
  • Organizer: 第12回日本RNA学会年会
  • Place of Presentation: 一橋記念講堂(東京都)
  • Year and Date: 20100727-20100729
• [Presentation] UVB暴露による培養水晶体上皮細胞での遺伝子発現変化 (2010)
  • Author(s): 長田ひろみ、吉竹佳の、石垣靖人、池田崇之、山代陽子、米倉秀人、佐々木洋
  • Organizer: 第114回日本眼科学会総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 20100415-20100418
• [Presentation] UVB暴露による培養水晶体上皮細胞での遺伝子発現変化 (2010)
  • Author(s): 長田ひろみ、吉竹佳の、石垣靖人、池田崇之、山代陽子、米倉秀人、佐々木洋
  • Organizer: 第36回水晶体研究会
  • Place of Presentation: 晴海グランドホテル(東京都)
  • Year and Date: 20100109-20100110
• [Presentation] 患者末梢血白血球RNAを用いたStickler症候群原因遺伝子COL2Alの新規3'splice site変異の同定 (2009)
  • Author(s): 米倉秀人、池田崇之、吉竹佳の、矢口裕基、長田ひろみ、佐々木洋
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド(神戸市)
  • Year and Date: 20091021-20091024
• [Presentation] 2型リアノジン受容体遺伝子にはGG-AG配列で切断されるイントロンが存在する (2009)
  • Author(s): 池田崇之、野口直哉、吉川雄朗、宇留野晃、那谷耕司、高澤伸、岡本宏、米倉秀人、菅原明
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド(神戸市)
  • Year and Date: 20091021-20091024
• [Presentation] Identification of the mutation site of Stickler syndrome causative gene in RNA extracted from peripheral blood leukocyte. (2009)
  • Author(s): Osada H, Yaguchi H, Yoshitake Y, Sasaki H, Yonekura H
  • Organizer: The Association for Research in Vision and Ophthalmology
  • Place of Presentation: Florida, USA
  • Year and Date: 20090503-20090507
• [Presentation] 末梢血白血球RNAを用いたStickler症候群原因遺伝子の変異部位の同定 (2009)
  • Author(s): 長田ひろみ、矢口裕基、佐々木洋、孫立、吉竹佳の、米倉秀人
  • Organizer: 第113回日本眼科学会総会
  • Place of Presentation: 東京国際フォーラム(東京都)
  • Year and Date: 20090416-20090419
• [Presentation] Micro-RNAs expressed in human microvascular endothelial cells. (2008)
  • Author(s): Yoshitake Y, Yonekura H
  • Organizer: The 33rd FEBS Congress & 11th IUBMB Conference
  • Place of Presentation: Athens, Greek
  • Year and Date: 20080628-20080703
• [Presentation] Regulatory mechanisms of alternative 3'-end processing of soluble VEGF receptor pre-mRNA in vascular endothelial cells. (2008)
  • Author(s): Yonekura H, Tsuruoka N, Yoshitake Y, Sun L, Watanabe T, Yamamoto H
  • Organizer: The 33rd FEBS Congress & 11th IUBMB Conference
  • Place of Presentation: Athens, Greek
  • Year and Date: 20080628-20080703
• [Presentation] ヒト骨芽細胞のコラーゲン産生およびラットの骨折治癒に対するコラーゲン・トリペプチドの効果 (2008)
  • Author(s): 酒井康夫、鶴岡直樹、吉竹佳の、米倉秀人、沼田徳暁
  • Organizer: 第62回日本栄養食糧学会
  • Place of Presentation: 女子栄養大学坂戸キャンパス(埼玉県坂戸市)
  • Year and Date: 20080502-20080504
• [Presentation] カルテオロール塩酸塩持続性点眼液の培養角膜細胞に対する影響 (2008)
  • Author(s): 矢口裕基,福田正道,高橋信夫,佐々木洋
  • Organizer: 第112回日本眼科学会総会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 20080417-20080420