Transcriptome analysis of pulmonary arterioles in interstitial pneumonia with pulmonary hypertension

• Project/Area Number: 26461187
• 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: Kyoto University
• Principal Investigator: Handa Tomohiro 京都大学, 医学研究科, 助教 (10432395)
• Co-Investigator(Kenkyū-buntansha): 佐藤 史顕 京都大学, 医学研究科, 准教授 (20467426) ; 伊達 洋至 京都大学, 医学研究科, 教授 (60252962)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 間質性肺疾患 / 肺高血圧症 / メトリックスメタロプロテアーゼ / マトリックスメタロプロテアーゼ / 間質性肺炎 / マイクロアレイ

Outline of Final Research Achievements

First, pathological grades of pulmonary arterioles in resected lungs from patients with interstitial pneumonias who underwent lung transplantation was assessed. In fibrotic areas, pulmonary arterial lesion was observed extensively, while pathological findings of pulmonary arteries were mild in less fibrotic areas. Secondary, RNA expression of matrix metalloproteinases (MMPs) was analyzed using whole lung specimen from IPF patients with and without pulmonary hypertension (PH). RNA expression of MMP-2 and MMP-9 were increased in patients with PH. In immunohistochemical analysis, their expression was mainly obserbed on lung epithelial cells, and their expression on pulmonary arterial cells were mild.

Research Products

• [Journal Article] Comprehensive evaluation of airway involvement in pulmonary sarcoidosis. (2017)
  • Author(s): Tanizawa K, Handa T, Nagai S, Niimi A, Oguma T, Kubo T, Ito Y, Aihara K, Ikezoe K, Matsumoto H, Hirai T, Chin K, Mishima M.
  • Journal Title: ERJ Open Res. Volume: 3 Issue: 1 Pages: 00105-2016
  • DOI: 10.1183/23120541.00105-2016
  • NAID: 120006360785
  • Peer Reviewed / Open Access
• [Journal Article] Respiratory diseases and vascular failure. (2017)
  • Author(s): Handa T, Tanizawa K.
  • Journal Title: Vascular failure Volume: 印刷中
  • NAID: 130006575557
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies. (2017)
  • Author(s): Tanizawa K, Handa T, Nakashima R, Kubo T, Hosono Y, Watanabe K, Aihara K, Ikezoe K, Sokai A, Nakatsuka Y, Taguchi Y, Hatta K, Noma S, Kobashi Y, Yoshizawa A, Oga T, Hirai T, Chin K, Nagai S, Izumi T, Mimori T, Mishima M.
  • Journal Title: Respir Med Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Platelet aggregability in patients with interstitial pneumonias. (2016)
  • Author(s): Handa T, Watanabe K, Tanizawa K, Oga T, Aihara K, Ikezoe K, Sokai A, Nakatsuka Y, Hirai T, Nagai S, Chin K, Horiuchi H, Mishima M.
  • Journal Title: Sarcoidosis Vasc Diffuse Lung Dis. Volume: 33 Pages: 143-150
  • Peer Reviewed
• [Journal Article] Serial perfusion in native lungs in patients with idiopathic pulmonary fibrosis and other interstitial lung diseases after single lung transplantation. (2016)
  • Author(s): Sokai A, Handa T, Chen F, Tanizawa K, Aoyama A, Kubo T, Ikezoe K, Nakatsuka Y, Oguma T, Hirai T, Nagai S, Chin K, Date H, Mishima M.
  • Journal Title: Clin Transplant. Volume: 30 Issue: 4 Pages: 407-414
  • DOI: 10.1111/ctr.12701
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Total lesion glycolysis as an IgG4-related disease activity marker. (2015)
  • Author(s): Nakatsuka Y, Handa T, Nakamoto Y, Nobashi T, Yoshihuji H, Tanizawa K, Ikezoe K, Sokai A, Kubo T, Hirai T, Chin K, Togashi K, Mimori T, Mishima M.
  • Journal Title: Mod Rheumatol. Volume: 25 Issue: 4 Pages: 579-584
  • DOI: 10.3109/14397595.2014.990674
  • Peer Reviewed
• [Journal Article] A toll-like receptor 3 single nucleotide polymorphism in Japanese patients with sarcoidosis. (2015)
  • Author(s): Ikezoe K, Handa T, Tanizawa K, Kubo T, Ito I, Sokai A, Nakatsuka Y, Nagai S, Izumi T, Mishima M
  • Journal Title: Tissue Antigens Volume: 85 Issue: 3 Pages: 204-208
  • DOI: 10.1111/tan.12535
  • Peer Reviewed / Open Access
• [Journal Article] Bone mineral density in patients with idiopathic pulmonary fibrosis. (2015)
  • Author(s): Ikezoe K, Handa T, Tanizawa K, Kubo T, Oguma T, Hamada S, Watanabe K, Aihara K, Sokai A, Nakatsuka Y, Muro S, Nagai S, Uno K, Chin K, Fukui M, Hirai T, Mishima M.
  • Journal Title: Respir Med. Volume: 109 Issue: 9 Pages: 1181-1187
  • DOI: 10.1016/j.rmed.2015.06.014
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Clinical impact of high-attenuation and cystic areas on computed tomography in fibrotic idiopathic interstitial pneumonias. (2015)
  • Author(s): Tanizawa K, Handa T, Nagai S, Hirai T, Kubo T, Oguma T, Ito I, Ito Y, Watanabe K, Aihara K, Ikezoe K, Oga T, Chin K, Izumi T, Mishima M.
  • Journal Title: BMC Pulm Med. Volume: 15 Issue: 1 Pages: 74-74
  • DOI: 10.1186/s12890-015-0069-0
  • NAID: 120005758261
  • Peer Reviewed / Open Access
• [Journal Article] Matrix metalloproteinase-10: a novel biomarker for idiopathic pulmonary fibrosis. (2015)
  • Author(s): Sokai A, Handa T, Tanizawa K, Oga T, Uno K, Tsuruyama T, Kubo T, Ikezoe K, Nakatsuka Y, Tanimura K, Muro S, Hirai T, Nagai S, Chin K, Mishima M.
  • Journal Title: Respir Res. Volume: 16 Issue: 1 Pages: 120-120
  • DOI: 10.1186/s12931-015-0280-9
  • NAID: 120005774669
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Treatment with methotrexate and low-dose corticosteroids in sarcoidosis patients with cardiac lesions. (2014)
  • Author(s): Nagai S, Yokomatsu T, Tanizawa K, Ikezoe K, Handa T, Ito Y, Ogino S, Izumi T.
  • Journal Title: Internal Medicine Volume: ５３ Pages: 427-433
  • NAID: 130003392671
  • Peer Reviewed
• [Journal Article] Videothoracoscopy-assisted surgical lung biopsy for interstitial lung diseases. (2014)
  • Author(s): Sonobe M, Handa T, Tanizawa K, Sato M, Sato T, Chen F, Omasa M, Bando T, Date H, Mishima M.
  • Journal Title: General Thoracic and Cardiovascular Surgery Volume: ６２ Issue: 6 Pages: 376-382
  • DOI: 10.1007/s11748-014-0383-0
  • Peer Reviewed
• [Journal Article] Total lesion glycolysis as an IgG4-related disease activity marker. (2014)
  • Author(s): Nakatsuka Y, Handa T, Nakamoto Y, Nobashi T, Yoshihuji H, Tanizawa K, Ikezoe K, Sokai A, Kubo T, Hirai T, Chin K, Togashi K, Mimori T, Mishima M.
  • Journal Title: Modern Rheumatology Volume: 30 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Clinical features of three cases with pulmonary alveolar proteinosis secondary to myelodysplastic syndrome developed during the course of Behçet's disease. (2013)
  • Author(s): Handa T, Nakatsue T, Baba M, Takada T, Nakata K, Ishii H
  • Journal Title: Respiratory Investigation Volume: 52 Issue: 1 Pages: 75-79
  • DOI: 10.1016/j.resinv.2013.05.005
  • Peer Reviewed / Open Access
• [Presentation] Serum Soluble IL-2 Receptor as a Biomarker in IgG4 Related Disease. (2017)
  • Author(s): Tomohiro Handa, Shoko Matsui, Hajime Yoshifuji, Kiminobu Tanizawa, Yuzo Kodama, Hiroshi Yamamoto, Seijiro Minamoto, Yuko Waseda, Kohei Ikezoe, Kazuo Chin, Toyohiro Hirai, Keishi Kubo, Tsuneyo Mimori, Tsutomu Chiba, Michiaki Mishima.
  • Organizer: International symposium on IgG4-RD & Associated Conditions
  • Place of Presentation: Lahaina, USA
  • Int'l Joint Research
• [Presentation] 脳死肺移植登録を行なった間質性肺疾患患者の臨床像と予後の検討 (2017)
  • Author(s): 池添 浩平，半田 知宏，谷澤 公伸，久保 武, 徳田 深作，中塚 賀也，山本 裕子，陳 豊史，青山 晃博，本山 秀樹，土屋 恭子，長井 苑子 ，平井 豊博，伊達 洋至，陳 和夫
  • Organizer: 第９回 呼吸機能イメージング研究会学術集会
  • Place of Presentation: 京都
• [Presentation] 間質性肺疾患患者の肺移植における予後評価と管理の実際 (2016)
  • Author(s): 半田知宏
  • Organizer: 第５６回日本呼吸器学会学術講演会
  • Place of Presentation: 京都
• [Presentation] 呼吸器疾患と血管病変 (2016)
  • Author(s): 半田知宏
  • Organizer: 第一回日本血管不全学会学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 特発性肺線維症患者における慢性腎臓病と予後の関連 (2016)
  • Author(s): 池添浩平、半田知宏、谷澤公伸、祖開暁彦、中塚賀也、久保武、平井豊博、田口善夫、長井苑子、陳和夫、三嶋理晃
  • Organizer: 第５６回日本呼吸器学会学術講演会
  • Place of Presentation: 京都
• [Presentation] A comprehensive evaluation of serum matrix metalloproteinases in idiopathic pulmonary fibrosis (2015)
  • Author(s): ２３.Akihiko Sokai, Tomohiro Handa, Kiminobu Tanizawa, Kazuko Uno, Toru Oga, Kohei Ikezoe, Yoshinari Nakatsuka, Toyohiro Hirai, Sonoko Nagai, Kazuo Chin, Michiaki Mishima.
  • Organizer: American Thoracic Society International Conference.
  • Place of Presentation: Denver, USA
  • Year and Date: 2015-05-17
  • Int'l Joint Research
• [Presentation] 特発性肺線維症におけるマトリックスメタロプロテイナーゼのバイオマーカーとしての有用性の検討 (2015)
  • Author(s): 5.祖開暁彦、半田知宏、谷澤公伸、小賀徹、宇野賀津子、池添浩平、中塚賀也、平井豊博、長井苑子、陳和夫、三嶋理晃
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-19
• [Presentation] 特発性肺線維症におけるマトリックスメタロプロテイナーゼのバイオマーカーとしての有用性の検討 (2015)
  • Author(s): 祖開暁彦、半田知宏、谷澤公伸、小賀徹、宇野賀津子、池添浩平、中塚賀也、平井豊博、長井苑子、陳和夫、三嶋理晃
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム、東京
  • Year and Date: 2015-04-17 – 2015-04-19
• [Presentation] 間質性肺炎に対する脳死片肺移植後残存肺の換気/血流の経時変化 (2015)
  • Author(s): 祖開暁彦、半田知宏、陳豊史、谷澤公伸、志熊啓、大畑惠資、久保武、池添浩平、中塚賀也、小熊毅、平井豊博、長井苑子、陳和夫、伊達洋至、三嶋理晃
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム、東京
  • Year and Date: 2015-04-17 – 2015-04-19
• [Presentation] Prognostic significance of asymmetrical distribution in acute exacerbation of interstitial pneumonia. (2014)
  • Author(s): Akihiko Sokai, Kiminobu Tanizawa, Tomohiro Handa, Takeshi Kubo, Kohei Ikezoe, Yoshinari Nakatsuka, Kensaku Aihara, Sonoko Nagai, Toyohiro Hirai, Kazuo Chin, Michiaki Mishima.
  • Organizer: European Respiratory Society Annual Congress
  • Place of Presentation: Munich, Germany
  • Year and Date: 2014-09-06 – 2014-09-10
• [Presentation] Serum prostaglandin F2α metabolite concentration in interstitial lung disease associated with polymyositis/ dermatomyositis. (2014)
  • Author(s): Yoshinari Nakatsuka, Tomohiro Handa, Ran Nakashima, Yuji Hosono, Toru Oga, Takeshi Kubo, Yoshio Taguchi, Kazuhiro Hatta, Akihiko Sokai, Kohei Ikezoe, Kiminobu Tanizawa, Toyohiro Hirai, Sonoko Nagai, Kazuo Chin, Tsuneyo Mimori, Michiaki Mishima.
  • Organizer: American Thoracic Society International Conference
  • Place of Presentation: SanDiego, USA
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] Bone mineral density assessed by computed tomography in patients with idiopathic pulmonary fibrosis. (2014)
  • Author(s): Kohei Ikezoe, Tomohiro Handa, Kizuku Watanabe, Kiminobu Tanizawa, Kensaku Aihara, Akihiko Sokai, Yoshinari Nakatsuka, Tsuyoshi Oguma, Takeshi Kubo, Shigeo Muro, Sonoko Nagai, Toyohiro Hirai, Kazuo Chin, Michiaki Mishima.
  • Organizer: American Thoracic Society International Conference
  • Place of Presentation: SanDiego, USA
  • Year and Date: 2014-05-16 – 2014-05-21
• [Book] Drug-Induced Lung Injury. (2017)
  • Author(s): Handa T, Yonezawa A, Azuma A
  • Publisher: Springer Press
• [Book] Idiopathic Pulmonary Fibrosis – Advances in Diagnostic Tools and Disease Management (2015)
  • Author(s): Tomohiro Handa, Arata Azuma
  • Total Pages: 240
  • Publisher: Springer