Development of treatment strategies for Pulmonary Alveolar Microlithiasis using an animal model

• Project/Area Number: 16K19460
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Sapporo Medical University
• Principal Investigator: Saito Atsushi 札幌医科大学, 医学部, 助教 (00768939)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 肺胞微石症 / 動物モデル / ナトリウムリン酸共輸送体 / 治療法開発 / 肺胞マクロファージ / 肺サーファクタント / マウスモデル / 低リン食治療法 / リン吸着剤 / 低リン食治療

Outline of Final Research Achievements

There was no effective treatment for alveolar microlithiasis. So we tried to developing the treatment strategies using our animal model in this research. LPD prevents progressive microlith accumulation in young Npt2b-/- mice and reverses stone burden in Npt2b-/- mice. On the other hands, there was a little side effect with this treatment. Additionally, Tomocube 3D microscope revealed that microlithes were present in alveolar macrophages from Npt2b-/- mice. Alveolar macrophage seems to play an important role in the metabolism of calcium phosphate microlithes.

Research Products

• [Int'l Joint Research] University of Cincinnati(米国)
• [Journal Article] Impaired diversity of the lung microbiome predicts progression of idiopathic pulmonary fibrosis (2018)
  • Author(s): Takahashi Youhei、Saito Atsushi、Chiba Hirofumi、Kuronuma Koji、Ikeda Kimiyuki、Kobayashi Tomofumi、Ariki Shigeru、Takahashi Motoko、Sasaki Yasushi、Takahashi Hiroki
  • Journal Title: Respir Res Volume: 19 Issue: 1 Pages: 34-34
  • DOI: 10.1186/s12931-018-0736-9
  • Peer Reviewed / Open Access
• [Journal Article] Surfactant protein A down-regulates epidermal growth factor receptor by mechanisms different from those of surfactant protein D (2017)
  • Author(s): Yoshihiro Hasegawa, Motoko Takahashi, Shigeru Ariki, Atsushi Saito, Yasuaki Uehara, Rina Takamiya, Koji Kuronuma, Hirofumi Chiba, Yuji Sakuma, Hiroki Takahashi, Yoshio Kuroki
  • Journal Title: J Bill Chem Volume: 292 Issue: 45 Pages: 18565-18576
  • DOI: 10.1074/jbc.m117.800771
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Serum surfactant protein D predicts the outcome of patients with idiopathic pulmonary fibrosis treated with pirfenidone (2017)
  • Author(s): Ikeda Kimiyuki、Shiratori Masanori、Chiba Hirofumi、Nishikiori Hirotaka、Yokoo Keiki、Saito Atsushi、Hasegawa Yoshihiro、Kuronuma Koji、Otsuka Mitsuo、Yamada Gen、Takahashi Hiroki
  • Journal Title: Respir Med. Volume: 131 Pages: 184-191
  • DOI: 10.1016/j.rmed.2017.08.021
  • Peer Reviewed
• [Journal Article] Disruption of the structural and functional features of surfactant protein A by acrolein in cigarette smoke (2017)
  • Author(s): Takamiya Rina、Uchida Koji、Shibata Takahiro、Maeno Toshitaka、Kato Masaki、Yamaguchi Yoshiki、Ariki Shigeru、Hasegawa Yoshihiro、Saito Atsushi、Miwa Soichi、Takahashi Hiroki、Akaike Takaaki、Kuroki Yoshio、Takahashi Motoko
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 8304-8304
  • DOI: 10.1038/s41598-017-08588-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Surfactant protein D inhibits activation of non-small cell lung cancer-associated mutant EGFR and affects clinical outcomes of patients (2017)
  • Author(s): Umeda Y、Hasegawa Y、Otsuka M、Ariki S、Takamiya R、Saito A、Uehara Y、Saijo H、Kuronuma K、Chiba H、Ohnishi H、Sakuma Y、Takahashi H、Kuroki Y、Takahashi M
  • Journal Title: Oncogene Volume: 36 Issue: 46 Pages: 6432-6445
  • DOI: 10.1038/onc.2017.253
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Surfactant protein A inhibits growth and adherence of uropathogenic Escherichia coli to protect the bladder from infection. (2017)
  • Author(s): Hashimoto J., Takahashi M., Satio A., Murata M., Kurimura Y., Nishitani C., Takamiya R., Uehara Y., Hasegawa Y., Hiyama Y., Sawada N., Takahashi S., Masumori N., Kuroki Y., Ariki S.
  • Journal Title: J. Immunol. Volume: 198 Issue: 7 Pages: 2898-2905
  • DOI: 10.4049/jimmunol.1502626
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Surfactant Protein A (SP-A) and SP-A-derived Peptide Attenuate Chemotaxis of Mast Cells Induced by Human β-defensin 3. (2017)
  • Author(s): Uehara Y., Takahashi M., Murata M., Saito A., Takamiya R., Hasegawa Y., Kuronuma K., Chiba H., Hashimoto J., Sawada N., Takahashi H., Kuroki Y., Ariki S.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 485 Issue: 1 Pages: 107-112
  • DOI: 10.1016/j.bbrc.2017.02.028
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mitogenic stimulation accelerates influenza-induced mortality by increasing susceptibility of alveolar type II cells to infection (2017)
  • Author(s): Nikolaidis Nikolaos M.、Noel John G.、Pitstick Lori B.、Gardner Jason C.、Uehara Yasuaki、Wu Huixing、Saito Atsushi、Lewnard Kara E.、Liu Huan、White Mitchell R.、Hartshorn Kevan L.、McCormack Francis X.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 114 Issue: 32
  • DOI: 10.1073/pnas.1621172114
  • Peer Reviewed
• [Journal Article] 肺サーファクタントタンパク質Aによるヒトβ－ディフェンシン３の機能調節 (2017)
  • Author(s): 有木茂、齋藤充史
  • Journal Title: 医療人育成センター紀要 第８号 平成２９年別冊 Volume: 8 Pages: 25-27
• [Journal Article] Pulmonary Alveolar Microlithiasis (2016)
  • Author(s): Saito, A. McCormack FX.
  • Journal Title: Clinics in Chest Medicine Volume: 37 Issue: 3 Pages: 441-441
  • DOI: 10.1016/j.ccm.2016.04.007
  • Int'l Joint Research
• [Presentation] Preclinical Studies Reveal Low Phosphate Diet as a Potential Therapy for Pulmonary Alveolar Microlithiasis (2017)
  • Author(s): Yasuaki Uehara , Nikolaos M. Nikolaidis , Atsushi Saito , Lori B. Pitstick , Huixing Wu , Hassane Amlal , Kathleen LaSance , Jason C. Woods , Jinbang Guo , Francis X. McCormack ,
  • Organizer: American Thoracic Society International Conference 2017
  • Int'l Joint Research
• [Presentation] 肺胞微石症の治療戦略 (2017)
  • Author(s): 齋藤充史
  • Organizer: 第53回日本肺サーファクタント・界面医学会学術研究会
  • Invited
• [Presentation] 呼吸器疾患に対するトランスレーショナルリサーチ～肺胞微石症を中心に～ (2017)
  • Author(s): 齋藤充史
  • Organizer: 第3回函館呼吸器フロンティアセミナー
  • Invited
• [Presentation] Pulmonary collectins provide a first line of defense against L. Pneumophila through inhibiting their type IV secretion system. (2017)
  • Author(s): 齋藤充史、有木茂、高橋弘毅、黒木由夫
  • Organizer: 欧州呼吸器学会 年次総会 2017
  • Int'l Joint Research
• [Presentation] Low Phosphate Diet Arrests and Reverses Lung Injury in Mice with Pulmonary Alveolar Microlithiasis (2016)
  • Author(s): Uehara Y, Saito A et al
  • Organizer: Rare Lung Diseases Research Conference 2016
  • Place of Presentation: Cincinnati, OH, USA
  • Year and Date: 2016-09-22
  • Int'l Joint Research
• [Presentation] 肺胞微石症モデルマウスを用いた病態解析 (2016)
  • Author(s): 齋藤充史
  • Organizer: 日本呼吸器学会学術講演会
  • Place of Presentation: 国立京都国際会館（京都市左京区）
  • Year and Date: 2016-04-08
• [Book] 分子呼吸器病学 (2017)
  • Author(s): 齋藤充史
  • Total Pages: 119
  • Publisher: 先端医学社
  • ISBN: 9784865501612