Development of novel serum marker and treatment for interstitilal lung diseases

• Project/Area Number: 25860649
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Nagasaki University
• Principal Investigator: KAKUGAWA Tomoyuki 長崎大学, 医歯薬学総合研究科(医学系), 助教 (90570953)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 特発性間質性肺炎 / 特発性肺線維症 / 急性増悪 / バイオマーカー / HSP47 / 急性間質性肺炎 / 薬剤性肺炎 / 急性呼吸窮迫症候群 / びまん性肺胞傷害 / 血清マーカー

Outline of Final Research Achievements

Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is essential for the biosynthesis and secretion of collagen molecules. Previous studies of various experimental diseases affecting the lung have shown that there is a close association between increased expression of HSP47 and excessive accumulation of collagen. In our study, serum HSP47 levels were significantly higher in patients with acute exacerbation of idiopathic pulmonary fibrosis, acute interstitial pneumonia, and drug induced lung disease with diffuse alveolar damage (DAD) pattern than those in patients with stable idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, and healthy volunteers, suggesting that underlying fibrogenic mechanisms involving HSP47 differ in the two conditions. Elevation of serum HSP47 might be due to distinctive characteristics of DAD. DAD changes may possibly induce leakage of HSP47 protein into the extracellular matrix.

Research Products

• [Journal Article] 急性間質性肺炎のバイオマーカー (2015)
  • Author(s): 角川智之
  • Journal Title: 分子呼吸器病 Volume: 19 Pages: 70-72
• [Journal Article] Serum heat shock protein 47 levels are elevated in acute interstitial pneumonia. (2014)
  • Author(s): Kakugawa, T., Yokota, S.I., Ishimatsu, Y., Hayashi, T., Nakashima, S., Hara, S., Sakamoto, N., Kubota, H., Mine, M., Matsuoka, Y., Mukae, H., Nagata, K., and Kohno, S.
  • Journal Title: BMC Pulm. Med. Volume: 14 Issue: 1 Pages: 48-48
  • DOI: 10.1186/1471-2466-14-48
  • NAID: 120006986596
  • Peer Reviewed
• [Journal Article] Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis (2013)
  • Author(s): Kakugawa, T., Yokota, S.I., Ishimatsu, Y., Hayashi. T., Nakashima, S., Hara, S., Sakamoto, N., Kubota, H., Mine, M., Matsuoka, Y., Mukae, H., Nagata, K., and Kohno, S.
  • Journal Title: Cell Stress Chaperones Volume: 18 Issue: 5 Pages: 581-590
  • DOI: 10.1007/s12192-013-0411-5
  • Peer Reviewed
• [Journal Article] Serum heat shock protein 47 levels in patients with drug-induced lung disease. (2013)
  • Author(s): Kakugawa, T., Yokota, S., Ishimatsu, Y., Hayashi, T., Nakashima, S., Hara, S., Sakamoto, N., Kubota, H., Mine, M., Y., Matsuoka, Y., Mukae, H., Nagata, K., and Kohno, S.
  • Journal Title: Respir. Res. Volume: 14 Issue: 1 Pages: 133-133
  • DOI: 10.1186/1465-9921-14-133
  • Peer Reviewed
• [Journal Article] Interstitial pneumonia associated with linear immunoglobulin A/immunoglobulin G bullous dermatosis. (2013)
  • Author(s): Kakugawa T, Tomimura S, Hayashi T, Sakamoto N, Ishimatsu Y, Mukae H, Kohno S.
  • Journal Title: Respiration Volume: 86 Issue: 4 Pages: 347-351
  • DOI: 10.1159/000351427
  • NAID: 120006986003
  • Peer Reviewed
• [Journal Article] Diffuse alveolar hemorrhage in a patient with ankylosing spondylitis. (2013)
  • Author(s): Hara S, Sakamoto N, Ishimatsu Y, Kakugawa T, Shimada M, Kohno S.
  • Journal Title: Internal Medicine Volume: 52 Pages: 1963-1966
  • NAID: 130003365770
  • Peer Reviewed
• [Journal Article] Clinical, serologic and magnetic resonance imaging of 3 cases of inflammatory myopathy with abundant macrophages in the japanese population. (2013)
  • Author(s): Hara S, Henmi T, Kawakami A, Fujikawa K, Mukae H, Ishimatsu Y, Sakamoto N, Kakugawa T, Kaji K, Fujimoto M, Kuwana M, Tsukada T, Satoh K, Motomura M, Tamai M, Nakamura H, Ida H, Hayashi T, Origuchi T, Eguchi K, Kohno S.
  • Journal Title: Rheumatology International Volume: 33 Pages: 1059-1064
  • NAID: 120006986730
  • Peer Reviewed
• [Presentation] Expression of heat shock protein 47 in chronic hypersensitivity pneumonitis (2015)
  • Author(s): Tomoyuki Kakugawa, Kazuhiro Tabata, Hirokazu Yura, Tatsuhiko Harada, Shota Nakashima, Atsuko Hara, Noriho Sakamoto, Yuji Ishimatsu, Junya Fukuoka, Shigeru Kohno
  • Organizer: European Respiratory Society International Congress 2015
  • Place of Presentation: アムステルダム（オランダ）
  • Year and Date: 2015-09-26
  • Int'l Joint Research
• [Presentation] 日常診療における新しいバイオマーカーの有用性・薬剤性肺障害のバイオマーカー (2014)
  • Author(s): 角川 智之
  • Organizer: 日本臨床薬理学会学術総会
  • Place of Presentation: ひめぎんホール（愛媛県松山市）
  • Year and Date: 2014-12-04 – 2014-12-06
• [Presentation] 薬剤性肺障害における血清中HSP47の検討 (2014)
  • Author(s): 角川 智之、横田 伸一、石松 祐二、中島 章太、原 信太郎、坂本 憲穂、三根眞理子 、永田 和宏、迎 寛、河野 茂
  • Organizer: 日本内科学会学術講演会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2014-04-11 – 2014-04-13
• [Presentation] Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis (2013)
  • Author(s): Tomoyuki Kakugawa, Shin-ichi Yokota, Yuji Ishimatsu, Shota Nakashima, Shintaro Hara, Noriho Sakamoto, Hiroshi Mukae, Kazuhiro Nagata and Shigeru Kohno
  • Organizer: 第５３回日本呼吸器学会学術講演会
  • Place of Presentation: 東京、東京国際フォーラム
• [Presentation] 薬剤性肺障害における血清中HSP47の検討 (2013)
  • Author(s): 角川 智之、横田 伸一、石松 祐二、中島 章太、原 信太郎、坂本 憲穂、三根眞理子、永田 和宏、迎 寛、河野 茂
  • Organizer: 第１１０回日本内科学会学術講演会
  • Place of Presentation: 東京、東京国際フォーラム
• [Presentation] 特発性間質性肺炎における血清中HSP47の検討 (2013)
  • Author(s): 東 祥嗣,角川 智之,横田 伸一,石松 祐二,中島 章太,原 信太郎,坂本 憲穂,永田 和宏,迎 寛,河野 茂
  • Organizer: 第１１０回日本内科学会学術講演会
  • Place of Presentation: 東京、東京国際フォーラム
• [Presentation] Serum heat shock protein 47 levels in patients with drug-induced lung disease (2013)
  • Author(s): Tomoyuki Kakugawa, Shin-ichi Yokota, Yuji Ishimatsu, Tomayoshi Hayashi, Shota Nakashima, Shintaro Hara, Noriho Sakamoto, Hiroshi Kubota, Mariko Mine, Yasuhiro Matsuoka, Hiroshi Mukae, Kazuhiro Nagata and Shigeru Kohno
  • Organizer: European Respiratory Society
  • Place of Presentation: スペイン、バルセロナ
• [Presentation] Serum heat shock protein 47 are elevated in acute interstitial pneumonia (2013)
  • Author(s): Yoshitsugu Higashi, Tomoyuki Kakugawa, Shin-ichi Yokota, Yuji Ishimatsu, Shota Nakashima, Shintaro Hara, Noriho Sakamoto, Hiroshi Kubota, Yasuhiro Matsuoka, Kazuhiro Nagata and Shigeru Kohno
  • Organizer: Asian Pacific Society of Respirology
  • Place of Presentation: 横浜、パシフィコ横浜