Serum extracellular matrix protein as a biomarker for acute exacerbation of interstitial pneumonia

• Project/Area Number: 16K09546
• 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: Fukushima Medical University
• Principal Investigator: Tanino Yoshinori 福島県立医科大学, 医学部, 准教授 (10443863)
• Co-Investigator(Kenkyū-buntansha): 棟方 充 福島県立医科大学, 医学部, 教授 (00209991) ; 王 新涛 福島県立医科大学, 医学部, 助教 (00448630) ; 海老名 雅仁 東北医科薬科大学, 医学部, 教授 (10280885)
• Research Collaborator: Leeming Diana Julie
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 細胞外マトリックス / 間質性肺炎急性増悪 / バイオマーカー / 特発性間質性肺炎 / 急性増悪 / 特発性肺線維症 / 予後予測因子

Outline of Final Research Achievements

Interstitial pneumonia is characterized by excessive accumulation of extracellular matrix (ECM) protein in interstitium, which is destructed in acute exacerbation (AE) leading to architectural distortion . In this study, we hypothesized that ECM protein levels in serum are changed in acute exacerbation of interstitial pneumonia (AE-IP), and examined the possibility that they are clinically helpful biomarkers in AE-IP.
Decorin, syndecan-4 and versican levels in serum were changed in both stable and AE phases, and related with prognosis in AE-IP. These results suggest that ECM protein levels in serum are possible clinically useful biomarkers in AE-IIP.

Academic Significance and Societal Importance of the Research Achievements

間質性肺炎は細胞外マトリックス(ECM)の改変を特徴としており、本研究ではその中でもプロテオグリカンに着目してして解析を行った。今回の検討では、プロテオグリカンであるdecorin、syndecan-4とversicanの血中濃度が間質性肺炎急性増悪の予後に関するバイオマーカーであることが示された。間質性肺炎急性増悪は、予後不良の間質性肺炎の予後を左右する病態であることから、その予後を予測できるバイオマーカーを確立することは間質性肺炎急性増悪に対する治療法検討に非常に有用であると考えられ、今後の臨床応用が期待される。

Research Products

• [Int'l Joint Research] Nordic Bioscience(デンマーク)
• [Int'l Joint Research] Nordic Bioscience(Denmark)
• [Int'l Joint Research] University of Washington(米国)
• [Journal Article] Interstitial Lung Disease Is a Possible Manifestation of Anti-signal Recognition Particle Antibody Syndrome (2018)
  • Author(s): Yoshinori Tanino
  • Journal Title: Internal Medicine Volume: 57 Issue: 14 Pages: 1957-1958
  • DOI: 10.2169/internalmedicine.0662-17
  • NAID: 130007404906
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2018-07-15
  • Peer Reviewed / Open Access
• [Journal Article] A Serological Biomarker of Versican Degradation is Associated with Mortality Following Acute Exacerbations of Idiopathic Interstitial Pneumonia (2018)
  • Author(s): Sand J, Tanino Y, Karsdal M, Nikaido T, Misa K, Sato Y, Togawa R, Wang X, Leeming D, Munakata M
  • Journal Title: Respir Res Volume: 19 Issue: 1 Pages: 82-82
  • DOI: 10.1186/s12931-018-0779-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Serum decorin is a potent prognostic biomarker in acute exacerbation of idiopathic pulmonary fibrosis (2018)
  • Author(s): Nikaido T, Tanino Y, Wang X, Sato Y, Togawa R, Kikuchi M, Misa K, Saito K, Fukuhara N, Kawamata T, Rikimaru M, Umeda T, Morimoto J, Koizumi T, Suzuki Y, Hirai K, Uematsu M, Minemura H, Fukuhara A, Sato S, Saito J, Yokouchi H, Kanazawa K, Shibata
  • Journal Title: J Thorac Dis Volume: 10 Issue: 9 Pages: 5346-58
  • DOI: 10.21037/jtd.2018.08.60
  • Peer Reviewed / Open Access
• [Journal Article] Does pirfenidone have anticancer effects in patients with idiopathic pulmonary fibrosis? (2018)
  • Author(s): Yoshinori Tanino
  • Journal Title: Respir Investig Volume: 56 Issue: 2 Pages: 95-96
  • DOI: 10.1016/j.resinv.2017.12.001
  • Peer Reviewed
• [Journal Article] Initial predictors of poor survival in myositis-associated interstitial lung disease: a multicenter cohort of 497 patients (2018)
  • Author(s): Shinji Sato, Kenichi Masui, Naoshi Nishina, Yasushi Kawaguchi, Atsushi Kawakami, Maasa Tamura, Kei Ikeda, Takahiro Nunokawa, Yoshinori Tanino, Katsuaki Asakawa, Yuko Kaneko, Takahisa Gono, Taro Ukichi, Shinjiro Kaieda, Taio Naniwa, Masataka Kuwana, et al
  • Journal Title: Rheumatology (Oxford) Volume: NA Issue: 7 Pages: 1212-1221
  • DOI: 10.1093/rheumatology/key060
  • Peer Reviewed
• [Journal Article] Baseline Serum Syndecan-4 Predicts Prognosis after the Onset of Acute Exacerbation of Idiopathic Interstitial Pneumonia (2017)
  • Author(s): Yuki Sato, Yoshinori Tanino, Xintao Wang, Takefumi Nikaido, Suguru Sato, Kenichi Misa, Ryuichi Togawa, Charles Frevert, Mitsuru Munakata
  • Journal Title: PLoS One Volume: 12 Issue: 5 Pages: e0176789-e0176789
  • DOI: 10.1371/journal.pone.0176789
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Involvement of midkine in the development of pulmonary fibrosis (2017)
  • Author(s): Kenichi Misa, Yoshinori Tanino, Xintao Wang, Takefumi Nikaido, Masami Kikuchi, Yuki Sato, Ryuichi Togawa, Mishie Tanino, Shinya Tanaka, Kenji Kadomatsu, Mitsuru Munakata
  • Journal Title: Physiol Rep Volume: 5
  • Peer Reviewed / Open Access
• [Journal Article] Midkineは肺の線維化を増強する (2017)
  • Author(s): 谷野功典、美佐健一、王 新涛、二階堂雄文、佐藤祐樹、東川隆一、谷野美智枝、棟方 充
  • Journal Title: 厚生労働科学研究委託業務 難治性疾患実用化研究事業 びまん性肺疾患に対するエビデンスを構築する新規戦略的研究 平成28年度研究報告書 Volume: NA Pages: 127-133
• [Journal Article] Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: an international case-cohort study. (2017)
  • Author(s): Walsh SLF, Maher TM, Kolb M, IPF Project Consortium
  • Journal Title: Eur Respir J Volume: 50 Issue: 2 Pages: 1700936-1700936
  • DOI: 10.1183/13993003.00936-2017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 間質性肺炎急性増悪における血中細胞外マトリックス蛋白のバイオマーカーとしての可能性 (2017)
  • Author(s): 谷野功典
  • Journal Title: 別冊BIO Clinica 慢性炎症と疾患 特集「呼吸器疾患と慢性炎症」 Volume: 6 Pages: 131-141
• [Journal Article] Basic FGFはBleomycinによる肺の線維化を抑制する (2017)
  • Author(s): 王 新涛、谷野功典、二階堂雄文、美佐健一、佐藤祐樹、東川隆一、鈴木康仁、植松 学、福原敦朗、佐藤 俊、斉藤純平、横内 浩、谷野美智枝、棟方 充
  • Journal Title: 分子呼吸器病学 Volume: 21 Pages: 112-115
• [Journal Article] Three cases of interstitial pneumonia with anti-signal recognition particle antibody (2017)
  • Author(s): Togawa R, Tanino Y, Nikaido T, Fukuhara N, Uematsu M, Misa K, Sato Y, Matsuda N, Sugiura Y, Namatame S, Kobayashi H, Hamaguchi Y, Fujimoto M, Kuwana M, Munakata M.
  • Journal Title: Allergology International Volume: 66 Issue: 3 Pages: 485-487
  • DOI: 10.1016/j.alit.2016.10.009
  • NAID: 130005858868
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 慢性間質性肺炎におけるBAL液スメアのパルミチン酸結晶の予後予測因子としての可能性 (2016)
  • Author(s): 谷野功典、福原奈緒子、立原素子、斉藤純平、佐藤俊、二階堂雄文、美佐健一、佐藤佑樹、東川隆一、鈴木康仁、植松学、福原敦朗、王新涛、石田卓、大波哲雄、棟方充
  • Journal Title: 厚生労働科学研究委託業務 難治性疾患実用化研究事業 びまん性肺疾患に対するエビデンスを構築する新規戦略的研究 平成27年度研究報告書 Volume: ー Pages: 125-128
• [Journal Article] Identification of Clinical Phenotypes in Idiopathic Interstitial Pneumonia with Pulmonary Emphysema (2016)
  • Author(s): Suguru Sato, Yoshinori Tanino, Kenichi Misa, Naoko Fukuhara, Takefumi Nikaido, Manabu Uematsu, Xintao Wang, Takashi Ishida, Mitsuru Munakata
  • Journal Title: Internal Medicine Volume: 55 Issue: 12 Pages: 1529-1535
  • DOI: 10.2169/internalmedicine.55.6009
  • NAID: 130005157666
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 肺胞蛋白症におけるBAL液中ヒアルロン酸の臨床的意義の検討 (2018)
  • Author(s): 東川隆一、二階堂雄文、佐藤佑樹、斉藤香恵、福原奈緒子、王新涛、福原敦朗、佐藤俊、金沢賢也、谷野功典
  • Organizer: 第58回日本呼吸器学会
• [Presentation] Hyaluronan in Bronchoalveolar Lavage Fluid from Patients with Autoimmune Pulmonary Alveolar Proteinosis (2018)
  • Author(s): Togawa R, Tanino Y, Nikaido T, Sato Y, Togawa R, Suzuki Y, Uematsu M, Fukuhara A, Sato S, Saito J, Shibata Y
  • Organizer: 23rd Congress of the APSR
  • Int'l Joint Research
• [Presentation] Combined Evaluation of Myositis-Specific Autonatibodies and Serum Conventional Biomarkers Is Useful for Stratification of Prognosis in Polymyositis/Dermatomyositis With Interstitial Lung Disease (2018)
  • Author(s): Takahisa Gono, Yasushi Kawaguchi, Atsushi Kawakami, Shinji Sato, Maasa Tamura, Kei Ikeda, Takahiro Nunokawa, Yoshinori Tanino, Katsuaki Asakawa, Yuko Kaneko, Naoshi Nishina, Kenichi Masui, Masataka Kuwana
  • Organizer: 2nd Global Conference on Myositis
  • Int'l Joint Research
• [Presentation] Influence of Season and Residential Environment on Development of Anti-Melanoma Differentiation-Associated Gene 5 Antibody-Positive Polymyositis/Dermatomyositis with Interstitial Lung Disease (2018)
  • Author(s): Naoshi Nishina, Shinji Sato, Yasushi Kawaguchi, Atsushi Kawakami, Maasa Tamura, Kei Ikeda, Takahiro Nunokawa, Yoshinori Tanino, Katsuaki Asakawa, Yuko Kaneko, Takahisa Gon, Kenichi Masui, Masataka Kuwana and JAMI investigators
  • Organizer: 2nd Global Conference on Myositis
  • Int'l Joint Research
• [Presentation] Biomarkers of Extracellular Matrix Remodeling are Associated with Acute Exacerbations of Idiopathic Interstitial Pneumonia (2018)
  • Author(s): Sand JMB, Tanino Y, Nikaido T, Misa K, Sato Y, Togawa R, Wang X, Leeming DJ, Munakata M
  • Organizer: ATS International Conference
  • Int'l Joint Research
• [Presentation] Biomarkers of Extracellular Matrix Remodeling are Associated with Acute Exacerbations of Idiopathic Interstitial Pneumonia (2018)
  • Author(s): J. Sand, P. Juhl, Y. Tanino, T. Nikaido, K. Misa, Y. Sato, R. Togawa, X. Wang, M. Karsdal, A. C. Bay-Jensen, D. Leeming, A. S. Siebuhr, M. Munakata
  • Organizer: EULAR Madrid 2017 Annual European Congress of Rheumatology
  • Int'l Joint Research
• [Presentation] Predictive Modeling of Mortality in Polymyositis/Dermatomyositis Patients with Interstitial Lung Disease Based on Combination of Serum Myositis-Specific Autoantibodies and Conventional Biomarkers (2018)
  • Author(s): Takahisa Gono, Kenichi Masui, Yasushi Kawaguchi, Kei Ikeda, Atsushi Kawakami, Maasa Tamura, Yoshinori Tanino, Takahiro Nunokawa, Yuko Kaneko, Shinji Sato, Katsuaki Asakawa, Naoshi Nishina, Masataka Kuwana
  • Organizer: ACR/ARHP Annual Meeting
  • Int'l Joint Research
• [Presentation] Serum Hyaluronan in Patients with Acute Exacerbation of Idiopathic Interstitial Pneumonia (2018)
  • Author(s): Takefumi Nikaido, Yosihnori Tanino, Xintao Wang, Yuki Sato, Ryuichi Togawa, Mitsuru Munakata
  • Organizer: 22nd Congress of the APSR
  • Int'l Joint Research
• [Presentation] Clinical Significance of SSA Antibody in Patients with ARS Antibody Positive Interstitial Pneumonia (2018)
  • Author(s): Yuki Sato, Yosihnori Tanino, Takefumi Nikaido, Ryuichi Togawa, Xintao Wang, Mitsuru Munakata
  • Organizer: 22nd Congress of the APSR
  • Int'l Joint Research
• [Presentation] Deficiency of Proteoglycan Syndecan-4 Exaggerates Viral Lung Inflammation (2018)
  • Author(s): Yosihnori Tanino, Xintao Wang, Takefumi Nikaido, Masami Kikuchi, Yuki Sato, Ryuichi Togawa, Tetsuhito Kojima, Mitsuru Munakata
  • Organizer: 22nd Congress of the APSR
  • Int'l Joint Research
• [Presentation] Serum Laminin α3 in Patients with Acute Exacerbation of Idiopathic Interstitial Pneumonia (2018)
  • Author(s): Ryuichi Togawa, Yosihnori Tanino, Xintao Wang, Takefumi Nikaido, Yuki Sato, Mitsuru Munakata
  • Organizer: 22nd Congress of the APSR
  • Int'l Joint Research
• [Presentation] 特発性間質性肺炎急性増悪における血清プロテオグリカンsyndecan-4の予後予測因子としての可能性 (2016)
  • Author(s): 佐藤佑樹、谷野功典、佐藤俊、二階堂雄文、美佐健一、東川隆一、斉藤香恵、福原奈緒子、斎藤純平、福原敦、植松学、鈴木康仁、王新涛、棟方充
  • Organizer: 日本結合組織学会
  • Place of Presentation: 長崎市
  • Year and Date: 2016-06-24
• [Presentation] Serum decorin as a possible prognostic biomarker in patients with acute exacerbation of idiopathic pulmonary fibrosis (2016)
  • Author(s): Nikaido T, Tanino Y, Fukuhara N, Misa K, Sato Y, Togawa R, Suzuki Y, Uematsu M, Fukuhara A, Sato S, Saito J, Wang X, Munakata M
  • Organizer: American Thoracic Society International Conference
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2016-05-17
  • Int'l Joint Research
• [Presentation] Serum Syndecan-1 in Patients with Acute Exacerbation of idiopathic Interstitial Pneumonia (2016)
  • Author(s): Togawa R, Tanino Y, Wang X, Nikaido T, Fukuhara N, Misa K, Sato Y, Suzuki Y, Uematsu M, Fukuhara A, Sato S, Saito J, Munakata M
  • Organizer: American Thoracic Society International Conference
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2016-05-15
  • Int'l Joint Research
• [Book] Multicentric Castleman Disease: Associated and Differential Disorders (2018)
  • Author(s): Yoshinori Tanino, Hiroyuki Minemura
  • Total Pages: 24
  • Publisher: Nova Science Publishers, Inc, NY
  • ISBN: 9781536130201
• [Book] 間質性肺炎急性増悪における血中細胞外マトリックス蛋白のバイオマーカーとしての可能性 (2017)
  • Author(s): 別冊BIO Clinica 慢性炎症と疾患 特集「呼吸器疾患と慢性炎症」
  • Publisher: 北隆社
• [Remarks] Nortic Bioscience
  • URL: https://www.nordicbioscience.com/biomarkers-research/