novel development research on the prevention and treatment of pulmonary fibrosis

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590936
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Hyogo College of Medicine
• Principal Investigator: TABATA Chiharu Hyogo College of Medicine, 医学部, 准教授 (90432393)
• Project Period (FY): 2008 – 2010
• Keywords: 非閉塞性肺疾患 / 肺線維症 / 呼吸器感染症 / その他

Research Abstract

We recently reported two substances (ATRA and thalidomide) had preventive effects on pulmonary fibrosis by inhibiting IL-6-dependent proliferation and TGF-β_1-dependent transdifferentiation of lung fibroblasts. Rheumatoid arthritis is a chronic autoimmune disorder, and its pathogenesis is also characterized by an association with several cytokines. It has been reported that Calpain, a calcium-dependent intracellular cysteine protease, plays an important role in the progression of Rheumatoid arthritis. In this study, we examined the preventive effect of Calpeptin, a calpain inhibitor, on bleomycin-induced pulmonary fibrosis.
Calpeptin histologically ameliorated bleomycin-induced pulmonary fibrosis in mice. Calpeptin decreased the expression of IL-6, TGF-β_1, angiopoietin-1, and collagen type Iα1 mRNA in mouse lung tissues. In vitro studies disclosed that Calpeptin reduced 1) production of IL-6, TGF-β_1, angiopoietin-1 and collagen synthesis from lung fibroblasts, and 2) both IL-6-dependent proliferation and angiopoietin-1-dependent migration of the cells, which could be the mechanism underlying the preventive effect of Calpeptin on pulmonary fibrosis.
These data suggest the clinical use of Calpeptin for the prevention of pulmonary fibrosis.

Research Products

• [Journal Article] The Calpain inhibitor Calpeptin Prevents Bleomycin-Induced Pulmonary Fibrosis in Mice. (2010)
  • Author(s): Tabata C, Tabata R, Nakano T
  • Journal Title: Clin Exp Immunol. 162 Pages: 560-7
  • Peer Reviewed
• [Journal Article] Novel clinical role of angiopoietin-1 in malignant pleural mesothelioma. (2010)
  • Author(s): Tabata C, Hirayama N, Tabata R, Yasumitsu A, Yamada S, Murakami A, Iida S, Tamura K, Fukuoka K, Kuribayashi K, Terada T, Nakano T
  • Journal Title: Eur Respir J. 36 Pages: 1099-105
  • Peer Reviewed
• [Journal Article] Clinical significance of serum VEGF in malignant pleural mesothelioma. (2010)
  • Author(s): Yasumitsu A, Tabata C, Tabata R, Hirayama N, Murakami A, Yamada S, Terada T, Iida S, Tamura K, Fukuoka K, Kuribayashi K, Nakano T
  • Journal Title: J Thorac Oncol. 5 Pages: 479-483
  • Peer Reviewed
• [Journal Article] Disappearing MDS-associated autoimmune hemolytic anemia in leukemic transformation. (2010)
  • Author(s): Tabata R, Tabata C, Omori K, Nagai T
  • Journal Title: Int Arch Allergy Immunol. 152 Pages: 407-412
  • Peer Reviewed
• [Journal Article] All-trans-retinoic acid inhibits tumour growth of malignant pleural mesothelioma in mice. (2009)
  • Author(s): Tabata C, Tabata R, Hirayama N, Yasumitsu A, Yamada S, Murakami A, Iida S, Tamura K, Terada T, Kuribayashi K, Fukuoka K, Nakano T
  • Journal Title: Eur Respir J. 34 Pages: 1159-1167
  • Peer Reviewed
• [Journal Article] Autoimmune Pancreatitis associated with Myelodysplastic Syndrome. (2009)
  • Author(s): Tabata R, Tabata C, Okamoto T, Omori K, Terada M, Nagai T
  • Journal Title: Int Arch Allergy Immunol. 151 Pages: 168-172
  • Peer Reviewed
• [Journal Article] Hemophagocytic syndrome in elderly patients with underlying autoimmune diseases. (2009)
  • Author(s): Tabata R, Tabata C, Terada M, Nagai T
  • Journal Title: Clin Rheumatol. 28 Pages: 461-464
  • Peer Reviewed
• [Journal Article] All-trans-retinoic acid attenuates radiation-induced intestinal fibrosis in mice. (2008)
  • Author(s): Okashi K, Kubo H, Nagayama S, Tabata C, Kadokawa Y, Hisamori S, Yonenaga Y, Fujimoto A, Mori A, Onodera H, Watanabe G, Sakai Y
  • Journal Title: J Surg Res. 150 Pages: 53-59
  • Peer Reviewed
• [Journal Article] All-trans-retinoic acid ameliorates carbon tetrachloride-induced liver fibrosis in mice through modulating cytokine production. (2008)
  • Author(s): Hisamori S, Tabata C, Kadokawa Y, Okoshi K, Tabata R, Mori A, Nagayama S, Watanabe G, Kubo H, Sakai Y
  • Journal Title: Liver Int. 28 Pages: 1217-1225
  • Peer Reviewed
• [Presentation] All-trans-retinoic acid inhibits tumour growth of malignant pleural mesothelioma in mice. (2010)
  • Author(s): Chiharu Tabata, Rie Tabata, Takashi Nakano
  • Organizer: European Respiratory Society
  • Place of Presentation: BARCELONA
  • Year and Date: 20100919-20100924
• [Remarks] ホームページ等
  • URL: http://www.hyo-med.ac.jp/department/rspr/