The development of a new therapy against interstitial lung disease using CNP

• Project/Area Number: 26861135
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory surgery
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Kimura Toru 国立研究開発法人国立循環器病研究センター, 研究所, 流動研究員 (90580796)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 肺外科 / 間質性肺炎 / 肺線維症 / 急性増悪 / ナトリウム利尿ペプチド

Outline of Final Research Achievements

We first developed a new mouse model of acute exacerbation (AE) of interstitial lung disease (ILD) for further investigation of prophylactic interventions. Secondly, our study revealed that C-type natriuretic peptide (CNP) had anti-inflammatory effect against LPS-induced acute lung injury mode (as one of the inflammatory stimulation models which induce AE) and anti-fibrotic effect against BLM-induced pulmonary fibrosis model. Additionally, our data suggest that CNP ameliorates bleomycin- induced pulmonary fibrosis by suppressing TGF-β signaling and myofibroblastic differentiation in lung fibroblasts. Therefore, we propose consideration of CNP for clinical application to treatment for pulmonary fibrosis and its exacerbation.

Research Products

• [Journal Article] C-type natriuretic peptide ameliorates pulmonary fibrosis by acting on lung fibroblasts in mice. (2016)
  • Author(s): Kimura T, Nojiri T, Hino J, Hosoda H, Miura K, Shintani Y, Inoue M, Zenitani M, Takabatake H, Miyazato M, Okumura M, Kangawa K.
  • Journal Title: Respiratory research Volume: 17 Issue: 1 Pages: 19-19
  • DOI: 10.1186/s12931-016-0335-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] C-type natriuretic peptide attenuates lipopolysaccharide-induced acute lung injury in mice (2015)
  • Author(s): Kimura T, Nojiri T, Hosoda H, Ishikane S, Shintani Y, Inoue M, Miyazato M, Okumura M, Kangawa K
  • Journal Title: J Surg Res Volume: 194 Issue: 2 Pages: 631-637
  • DOI: 10.1016/j.jss.2014.11.023
  • Peer Reviewed / Open Access
• [Journal Article] Protective effects of C-type natriuretic peptide on cisplatin-induced nephrotoxicity in mice (2015)
  • Author(s): Kimura, T., Nojiri, T., Hosoda, H., Ishikane, S., Shintani, Y., Inoue, M., Miyazato, M., Okumura, M., Kangawa, K.
  • Journal Title: Cancer Chemotherapy and Pharmacology Volume: 75(5) Issue: 5 Pages: 1057-1063
  • DOI: 10.1007/s00280-015-2734-7
  • Peer Reviewed / Open Access
• [Journal Article] Exacerbation of bleomycin-induced injury by lipopolysaccharide in mice: establishment of a mouse model for acute exacerbation of interstitial lung diseases. (2015)
  • Author(s): Kimura T, Nojiri T, Hosoda H, Shintani Y, Inoue M, Miyazato M, Okumura M, Kangawa K.
  • Journal Title: European journal of cardio-thoracic surgery Volume: 48 Issue: 4 Pages: e85-e91
  • DOI: 10.1093/ejcts/ezv261
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] C型ナトリウム利尿ペプチドによるヒト肺線維芽細胞の活性化抑制効果 (2015)
  • Author(s): 木村亨, 野尻崇, 細田洋司, 三浦浩一, 新谷康, 川村知裕, 舟木壮一郎, 別所俊哉, 井上匡美, 南正人, 寒川賢治, 奥村明之進
  • Organizer: 日本肺癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2015-11-26
• [Presentation] C-type natriuretic peptide atteuates bleomycin-induced fibrosis and inflammation in murine lung (2015)
  • Author(s): Toru Kimura, Takashi Nojiri, Hihoshi Hosoda, Yasushi Shintani, Masayoshi Inoue, Mikiya Miyazato, Meinoshin Okumura, Kenji Kangawa
  • Organizer: 16th World Conference on Lung Cancer
  • Place of Presentation: Denver, USA
  • Year and Date: 2015-09-06
  • Int'l Joint Research
• [Presentation] CNP attenuates renal toxicity induced by cisplatin in murine kidney (2015)
  • Author(s): Toru Kimura, Takashi Nojiri, Hihoshi Hosoda, Mikiya Miyazato, Kenji Kangawa
  • Organizer: 7th International Conference on cGMP
  • Place of Presentation: Trier, Germany
  • Year and Date: 2015-06-19
  • Int'l Joint Research
• [Presentation] 間質性肺炎急性増悪モデルマウスの作製と新規治療法の探索 (2015)
  • Author(s): 木村亨, 野尻崇, 細田洋司, 日野純, 新谷康, 川村知裕, 舟木壮一郎, 別所俊哉, 井上匡美, 南正人, 寒川賢治, 奥村明之進
  • Organizer: 関西胸部外科学会
  • Place of Presentation: 岡山
  • Year and Date: 2015-06-11
• [Presentation] Establishment of a new mouse model for postoperative acute exacerbation in interstitial lung diseases (2015)
  • Author(s): Toru Kimura, Takashi Nojiri, Hihoshi Hosoda, Yasushi Shintani, Masayoshi Inoue, Mikiya Miyazato, Meinoshin Okumura, Kenji Kangawa
  • Organizer: 23rd European Conference on General Thoracic Surgery
  • Place of Presentation: Lisbon-Portugal
  • Year and Date: 2015-05-31
  • Int'l Joint Research
• [Presentation] C-type natriuretic peptide atteuates acute and chronic inflammatory reactions in murine lung (2015)
  • Author(s): Toru Kimura
  • Organizer: Thoracic Surgery Seminar in Kyoto
  • Place of Presentation: 京都
  • Year and Date: 2015-05-16
  • Int'l Joint Research
• [Presentation] 肺線維症に対するC型ナトリウム利尿ペプチドの効果 (2015)
  • Author(s): 木村亨, 野尻崇, 細田洋司, 三浦浩一, 新谷康, 川村知裕, 舟木壮一郎, 井上匡美, 南正人, 寒川賢治, 奥村明之進
  • Organizer: 日本呼吸器外科学会
  • Place of Presentation: 香川
  • Year and Date: 2015-05-14
• [Presentation] シスプラチン誘発急性腎障害モデルマウスに対するC型ナトリウム利尿ペプチドの腎保護効果についての検討 (2014)
  • Author(s): 木村亨, 野尻崇, 細田洋司, 新谷康, 川村知裕, 舟木壮一郎, 井上匡美, 南正人, 寒川賢治, 奥村明之進
  • Organizer: 第55回日本肺癌学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-11-14 – 2014-11-15
• [Presentation] Bleomycin誘発肺障害マウスへのLipopolysaccharide吸入による間質性肺炎・肺線維症急性増悪モデルの作製 (2014)
  • Author(s): 木村亨, 野尻崇, 細田洋司, 新谷康, 川村知裕, 舟木壮一郎, 中桐伴行, 井上匡美, 南正人, 寒川賢治, 奥村明之進
  • Organizer: 第67回日本胸部外科学会定期学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-30 – 2014-10-02
• [Presentation] Protective effect of C-type natriuretic peptide on lipopolysaccharide-induced acute lung injury in mice (2014)
  • Author(s): Toru Kimura, Takashi Nojiri, Hihoshi Hosoda, Yasushi Shintani, Shin Ishikane, Masayoshi Inoue, Mikiya Miyazato, Meinoshin Okumura, Kenji Kangawa
  • Organizer: The Conference on Bioactive Peptides for Cell-Cell Communication 2014
  • Place of Presentation: 京都
  • Year and Date: 2014-09-10 – 2014-09-11
• [Presentation] Protective effect of C-type natriuretic peptide on lipopolysaccharide-induced acute lung injury in mice (2014)
  • Author(s): Toru Kimura, Takashi Nojiri, Hihoshi Hosoda, Yasushi Shintani, Shin Ishikane, Masayoshi Inoue, Mikiya Miyazato, Meinoshin Okumura, Kenji Kangawa
  • Organizer: 22th European Conference on General Thoracic Surgery
  • Place of Presentation: Copenhagen
  • Year and Date: 2014-06-15 – 2014-06-18
• [Presentation] Lipopolysaccaride誘発急性肺障害モデルマウスに対するC型ナトリウム利尿ペプチドの効果 (2014)
  • Author(s): 木村亨, 野尻崇, 細田洋司, 新谷康, 川村知裕, 舟木壮一郎, 中桐伴行, 井上匡美, 澤端章好, 南正人, 寒川賢治, 奥村明之進
  • Organizer: 第31回日本呼吸器外科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-29 – 2014-05-30