Molecular mechanism of alveolar formation

• Project/Area Number: 23659428
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Chiba University
• Principal Investigator: HATANO Masahiko 千葉大学, 大学院・医学研究院, 教授 (20208523)
• Co-Investigator(Kenkyū-buntansha): ARIMA Masafumi 千葉大学, 大学院・医学研究院, 講師 (00202763)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 閉塞性肺疾患 / DA-Raf / 肺胞形成 / 筋繊維芽細胞 / II型肺胞細胞 / ノックアウトマウス / Ras/ERKシグナル / 2型肺胞上皮細胞

Research Abstract

We analyzed molecular mechanism of alveolization using DA-Raf KO mice. DA-RafKO mice have defects in alveolar septum formation and alveolization during neonatalperiods. Myofibroblast differentiation was severely blocked in P2～P5 of development inthe KO mice. DA-Raf mRNA is highly expressed in type II alveolar epithelial cells(AEII). Lineage trace experiment using SPC-CreER and LacZ floxed mice revealedthat AEII cells did not differentiate to myofibroblasts in neonatal periods. Thus, DARafregulates myofibroblast differentiation by suppressing Ras-ERK cascade in noncellautonomousmanner in neonatal period of lung development.

Research Products

• [Journal Article] Integration of the mouse sperm fertilization-related protein equatorin into the acrosome during spermatogenesis as revealed by super-resolution and immunoelectron microscopy (2013)
  • Author(s): Ito C, Yamatoya K, Yoshida K, Fujimura L, Hatano M, Miyado K, Toshimori K
  • Journal Title: Cell Tissue Res Volume: 352(3) Issue: 3 Pages: 739-750
  • DOI: 10.1007/s00441-013-1605-y
  • Peer Reviewed
• [Journal Article] ADAR1 induces adenosine-targeted DNA mutations in senescent Bcl6-deficient cells (2013)
  • Author(s): Tsuruoka, N., Arima, M., Yoshida, N., Okada, S., Sakamoto, A., Hatano, M., Satake, H., Arguni, E., Wang, J.-Y., Yang, J.-H., Nishikura, K., Sekiya, S., Shozu, M. and Tokuhisa, T.
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 2 Pages: 826-836
  • DOI: 10.1074/jbc.m112.365718
  • Peer Reviewed
• [Journal Article] Generation of tissue-specific H-2K(d) transgenic mice for the study of K(d)-restricted malaria epitope-specific CD8(+) T-cell responses in vivo (2013)
  • Author(s): Huang J, Li X, Kohno K, Hatano M, Tokuhisa T, Murray PJ, Brocker T, and Tsuji M
  • Journal Title: J. Immunol. Methods Volume: 387 Issue: 1-2 Pages: 254-261
  • DOI: 10.1016/j.jim.2012.10.019
  • Peer Reviewed
• [Journal Article] BAZF, a novel component of cullin3-based E3 ligase complex, mediates VEGFR and Notch cross-signalling in angiogenesis (2012)
  • Author(s): Ohnuki H, Inoue H, Takemori N, Nakayama H, Sakaue T, Fukuda S, Miwa D, Nishiwaki E, Hatano M, Tokuhisa T, Endo Y, Nose M, and Higashiyama S
  • Journal Title: Blood Volume: 119 Issue: 11 Pages: 2688-2698
  • DOI: 10.1182/blood-2011-03-345306
  • Peer Reviewed
• [Journal Article] BAZF, a novel component of cullin3-based E3 ligase complex, mediates VEGFR and Notch cross-signaling in angiogenesis (2012)
  • Author(s): Ohnuki H, Inoue H, Takemori N, Nakayama H, Sakaue T, Fukuda S, Miwa D, Nishiwaki E, Hatano M, Tokuhisa T, Endo Y, Nose M, Higashiyama S
  • Journal Title: Blood Volume: 119 Pages: 2688-98
  • Peer Reviewed
• [Journal Article] Role of Prickle1 and Prickle2 in neurite outgrowth in murine neuroblastoma cells (2012)
  • Author(s): Fujimura L, Hatano M
  • Journal Title: Methods Mol Biol Volume: 838 Pages: 173-85
  • Peer Reviewed
• [Journal Article] Bcl6 in pulmonary epithelium coordinately controls the expression of the CC-type chemokine genes and attenuates allergic airway inflammation (2011)
  • Author(s): Seto T, et al
  • Journal Title: Clin Exp Allergy Volume: 41 Issue: 11 Pages: 1568-78
  • DOI: 10.1111/j.1365-2222.2011.03836.x
  • Peer Reviewed
• [Journal Article] Bcl6 in pulumonary epithelium coordinately controls the expression of the CC-type chemokine genes and attenuates allergic airway inflammation (2011)
  • Author(s): Seto T, Yoshitake M, Ogasawara T, Ikari J, Sakamoto A, Hatano M, Hirata H, Fukuda T, Kuriyama T, Tatsumi K, Tokuhisa T, Arima M
  • Journal Title: Clin Exp Allergy Volume: 41 Pages: 1568-78
  • Peer Reviewed
• [Presentation] Ras-ERK カスケードのアンタゴニストDA-Raf は肺胞形成を制御している (2012)
  • Author(s): 渡邊-高野晴子, 幡野雅彦, 坂本明美, 高野和儀, 徳久剛史, 遠藤剛
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-16
• [Presentation] Nczf disruption results in early embryonic lethality by disregurating p27 expression (2012)
  • Author(s): 寺竹洋一、長谷川勇太,藤村理紗、高野晴子、徳久剛史,幡野雅彦
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-11
• [Presentation] Nitric oxide derived from enteric neurons regulates intestinal barrier function (2012)
  • Author(s): 藤村理紗、坂本明美、有馬雅史、徳久剛史、幡野雅彦
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-07
• [Presentation] Bcl6 is required for ICOSL expression on activated B cells (2012)
  • Author(s): 飯島裕太、Pan Jing、河野麻仁、有馬雅史、幡野雅彦、徳久剛史、坂本明
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-07
• [Presentation] A role of Bcl6 in differentiation of memory precursor CD8 T cells (2012)
  • Author(s): Pan Jing、坂本明美、河野麻仁、有馬雅史、幡野雅彦、徳久剛史
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-06
• [Presentation] Role of IL-33 in a suppressive function of Bcl6 for IL-4 production by memory Th2 cells (2012)
  • Author(s): 有馬雅史、谷口俊文、藤村理紗、坂本明美、幡野雅彦、徳久剛史
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-05
• [Presentation] Regulation of SLAM-associated protein in follicular helper T cells by Bcl6 (2012)
  • Author(s): 谷口俊文、坂本明美、幡野雅彦、松本健司、斎藤博久、徳久剛史、有馬雅史
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-05
• [Presentation] Roles of ADAR1 in somatic hypermutation and class switch recombination in germinal center B cells. (2012)
  • Author(s): 鶴岡信栄、吉田信也、成毛耕儀、有馬雅史、坂本明美、幡野雅彦、王継揚、徳久剛史
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-05
• [Presentation] Phf11 promotes IgE class switch recombination in activated B cells (2012)
  • Author(s): 山本拓也、谷口俊文、稲嶺絢子、藤村理紗、坂本明美、幡野雅彦、徳久剛史、有馬雅史
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-05
• [Presentation] Nczf disruption results in early embryonic lethality by disregurating p27 expression (2011)
  • Author(s): 寺竹洋一、長谷川勇太,藤村理紗、高野晴子、徳久剛史,幡野雅彦
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-16
• [Presentation] Ncx 欠損は腸管上皮のバリア異常により腸炎を発症する (2011)
  • Author(s): 藤村理紗、坂本明美、有馬雅史、徳久剛史、幡野雅彦
  • Organizer: 第40回日本免疫学
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-28
• [Presentation] エフェクターとセントラルメモリーの分化はナイーブCD4 T細胞の段階で決定されている (2011)
  • Author(s): 河野麻仁、坂本明美、Pan Jing、山下公大、稲毛寿美奈、有馬雅史、幡野雅彦、徳久剛史
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-28
• [Presentation] 長期生存型抗体産生細胞分化におけるIL-21 シグナルの役割 (2011)
  • Author(s): 稲嶺絢子、有馬雅史、吉田信也、坂本明美、幡野雅彦、岡本美孝、徳久剛史
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-28
• [Presentation] 有馬雅史好塩基球のTH2サイトカイン遺伝子発現制御におけるGATA2 の役割 (2011)
  • Author(s): 花角尚子、稲嶺絢子、小橋優子、高野晴子、藤村理紗、坂本明美、幡野雅彦、徳久剛史、有馬雅史
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-28
• [Presentation] 樹状細胞によるTH2 誘導サイトカイン産生に対するBcl6 の抑制作用 (2011)
  • Author(s): 小橋優子、稲嶺絢子、稲毛寿美奈、高野晴子、藤村理紗、坂本明美、幡野雅彦、徳久剛史、有馬雅史
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-28
• [Presentation] Bcl6はDCからのTNFa 産生を抑制することによりTH分化を制御する (2011)
  • Author(s): 稲毛寿美奈、坂本明美、河野麻仁、Pan Jing、有馬雅史、幡野雅彦、徳久剛
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-28
• [Presentation] メモリープリカーサーCD8 T 細胞分化におけるBcl6の役割の解析 (2011)
  • Author(s): Pan Jing、坂本明美、河野麻仁、稲毛寿美奈、有馬雅史、幡野雅彦、徳久剛史
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-28
• [Presentation] TFH 細胞とTH2 細胞におけるIL-4 は異なる調節機構で産生される (2011)
  • Author(s): 有馬雅史、稲嶺絢子、小橋優子、坂本明美、幡野雅彦、久保允人、徳久剛史
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-27
• [Presentation] ADAR1 はBcl6 欠損細胞において体細胞突然変異を誘導する (2011)
  • Author(s): 鶴岡信栄、有馬雅史、坂本明美、幡野雅彦、徳久剛史
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-27
• [Presentation] 胚中心B 細胞のA-T 塩基対変異におけるADAR1 の役割 (2011)
  • Author(s): 吉田信也、鶴岡信栄、成毛耕儀、有馬雅史、高野晴子、坂本明美、幡野雅彦、徳久剛史
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-27
• [Presentation] Nczf disruption results in early embryonic lethality by disregulating p27 expression (2011)
  • Author(s): 寺竹洋一，長谷川勇太、藤村理紗、高野晴子、徳久剛史，幡野雅彦
  • Organizer: 第３４回日本分子生物学会
  • Place of Presentation: 横浜
• [Presentation] Ncx欠損は腸管上皮バリアの異常により腸炎を発症する (2011)
  • Author(s): 藤村理紗、坂本明美、有馬雅史、徳久剛史、幡野雅彦
  • Organizer: 第４０回日本免疫学会
  • Place of Presentation: 千葉
• [Presentation] Ras-ERKカスケードのアンタゴニストDA-Rafは肺胞形成を制御している
  • Author(s): 渡邊-高野 晴子, 幡野 雅彦, 坂本 明美, 高野 和儀, 徳久 剛史, 遠藤 剛
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] Nczf disruption results in early embryonic lethality by disregulating p27 expression.
  • Author(s): 寺竹洋一、長谷川勇太，藤村理紗、高野晴子、徳久剛史，幡野雅彦
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
• [Presentation] Nitric oxide derived from enteric neurons regulates intestinal barrier function.
  • Author(s): 藤村理紗、坂本明美、有馬雅史、徳久剛史、幡野雅彦
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸
• [Book] "Methods in Molecular Biology"Edited by Chen P. and Turksen K. Springer (2012)
  • Author(s): Fujimura L. and Hatano M.
  • Publisher: Role of Prickle1 and Prickle2 in neurite outgrowth in murine neuroblastoma cells. Planar cell polarity methods and protocols.
• [Remarks]