The role of new lipid mediator in the pathogenesis of interstitial pneumonia

• Project/Area Number: 15K09180
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kagoshima University
• Principal Investigator: WATANABE Masaki 鹿児島大学, 医歯学総合研究科, 特任助教 (90398298)
• Co-Investigator(Kenkyū-buntansha): 井上 博雅 鹿児島大学, 医歯学域医学系, 教授 (30264039)
• Co-Investigator(Renkei-kenkyūsha): OIKE Yuichi 熊本大学, 大学院生命科学研究部・分子遺伝学分野 (90312321)
• Research Collaborator: MOTOKAWA Ikuyo
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 間質性肺炎 / アンジオポエチン様因子2 / 肺線維症 / アンジオポエチン様因子２ / アンジオポエチン様因子

Outline of Final Research Achievements

Angiopoietin-like protein 2 (ANGPTL2) is a chronic inflammatory mediator that is associated with various pathologies. However, little is known about its activity in lung. We observed abundant ANGPTL2 expression in both alveolar epithelial type I and type II cells and in resident alveolar macrophages under normal conditions. Bleomycin-treated wild type mice showed specifically upregulated ANGPTL2 expression in areas of severe interstitial pneumonia, while Angptl2 KO mice developed more severe lung fibrosis than did comparably treated wild-type mice. Angptl2 loss in myeloid cells does not underlie fibrotic phenotypes. We conclude that Angptl2 deficiency in lung epithelial cells and resident alveolar macrophages causes severe lung fibrosis seen following bleomycin treatment, suggesting that ANGPTL2 derived from these cell types plays a protective role against fibrosis in lung.

Research Products

• [Journal Article] Regulation of LOXL2 and SERPINH1 by antitumor microRNA-29a in lung cancer with idiopathic pulmonary fibrosis (2016)
  • Author(s): Kamikawaji K, Seki N, Watanabe M, Mataki H, Kumamoto T, Takagi K, Mizuno K, Inoue H
  • Journal Title: J Hum Genet Volume: 61 Issue: 12 Pages: 985-993
  • DOI: 10.1038/jhg.2016.99
  • NAID: 40021022822
  • Peer Reviewed
• [Journal Article] Interstitial pneumonia induced by bleomycin treatment is exacerbated in Angptl2-deficient mice (2016)
  • Author(s): Motokawa I, Endo M, Terada K, Horiguchi H, Miyata K, Kadomatsu T, Morinaga J, Sugizaki T, Ito T, Araki K, Morioka MS, Manabe I, Samukawa T, Watanabe M, Inoue H, Oike Y.
  • Journal Title: American Journal of Physiology. Lung Cellular and Molecular Physiology Volume: 311 Issue: 4 Pages: 704-713
  • DOI: 10.1152/ajplung.00005.2016
  • Peer Reviewed
• [Journal Article] An inhaled phosphodiesterase 4 inhibitor E6005 suppresses pulmonary inflammation in mice (2015)
  • Author(s): Kubota S, Watanabe M, Shirato M, Okuno T, Higashimoto I, Machida K, Yokomizo T, Inoue H
  • Journal Title: Eur J Pharmacol Volume: 768 Pages: 41-48
  • DOI: 10.1016/j.ejphar.2015.10.013
  • Peer Reviewed / Acknowledgement Compliant