COPD endotype investigated through the comparison between mice and human study.
| Project/Area Number |
16K09536
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Nara Medical University (2018)
Kyoto University (2016-2017) |
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Principal Investigator |
Muro Shigeo 奈良県立医科大学, 医学部, 教授 (60344454)
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| Co-Investigator(Kenkyū-buntansha) |
佐藤 晋 京都大学, 医学研究科, 助教 (40378691)
佐藤 篤靖 京都大学, 医学研究科, 助教 (30706677)
田辺 直也 京都大学, 医学研究科, 特定助教 (30805817)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | COPD / 肺気腫 / フラクタル / 形態学 / 動物モデル / プロテアーゼ / 画像解析 / 蛋白分解酵素 / 胸部CT / 喫煙マウスモデル / 臨床呼吸器学 / 画像・形態評価 / エンドタイプ / 形態 / 酸化ストレス |
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| Outline of Final Research Achievements |
We have been developed two-dimensional CT image analysis human COPD cases and reported that the distribution pattern of emphysematous changes has a certain rule (fractal nature). In this study, three-dimensional CT image analysis revealed that when the emphysematous change in the whole lung progressed to some extent, a large emphysematous lesion that deviated from fractality property suddenly appeared, suggesting that mechanisms during lung parenchymal destruction may be different between early emphysema and progressed diseases. To elucidate molecular mechanisms in the process of lung parenchymal destruction, we developed a model mouse in which alveolar destruction progresses by proteolytic enzyme excess. We need to continue analyze whether it is possible to elucidate the detailed mechanism of the change occurring in human lung through the comparison of the morphological change in the mice pathology.
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| Academic Significance and Societal Importance of the Research Achievements |
超高齢化が進み、慢性閉塞性肺疾患（COPD)の罹患率は高く、死亡数は膨大である。日本人COPDの多くは肺気腫型であるが、肺気腫を修復する治療は存在せず、治療開発のために、肺胞破壊の機序を解明することが必要である。しかしヒトでは定期的に肺の組織を取り出して観察することは不可能であるため、胸部CTなどの非侵襲的検査から、肺胞破壊の機序を推定し、薬剤治療の標的を決定する必要がある。本研究では、ヒト胸部CT画像の経年的変化から、肺胞破壊の様式が軽症と重症で異なる可能性を見いだした。同時に、マウス実験から肺胞細胞を分解する蛋白分解酵素過剰モデルを作成し、ヒト肺との形態学的類似性の検討を今後の課題とした。
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Complementary regional heterogeneity information from COPD patients obtained using oxygen-enhanced MRI and chest CT2018
Author(s)
Fuseya Y, Muro S, Sato S, Tanabe N, Sato A, Tanimura K, Hasegawa K, Uemasu K, Kubo T, Kido A, Fujimoto K, Fushimi Y, Kusahara H, Sakashita N, Ohno Y, Togashi K, Mishima M, Hirai T.
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Journal Title
PLoS One
Volume: 30
Issue: 8
Pages: e0203273-e0203273
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Radiologic and Functional Analysis of Compensatory Lung Growth After Living-Donor Lobectomy.2018
Author(s)
Shikuma K, Chen-Yoshikawa TF, Oguma T, Kubo T, Ohata K, Hamaji M, Kawaguchi A, Motoyama H, Hijiya K, Aoyama A, Matsumoto H, Muro S, Date H.
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Journal Title
Ann Thorac Surg
Volume: 105
Pages: 909-914
Related Report
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[Journal Article] Risks and Cough-Aggravating Factors in Prolonged Cough: Epidemiological Observations from the Nagahama Cohort Study.2017
Author(s)
Matsumoto H, Izuhara Y, Niimi A, Tabara Y, Nagasaki T, Kanemitsu Y, Murase K, Oguma T, Ito I, Muro S, Sekine A, Matsuda F, Kosugi S, Nakayama T, Chin K, Mishima M; Nagahama Study Collaboration Group..
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Journal Title
Ann Am Thorac Soc.
Volume: Feb 10.
Issue: 5
Pages: 698-705
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Impacts of Smoking and Serum IgE Level on Blood Eosinophil Counts in the General Population: The Nagahama Study2018
Author(s)
Sunadome H,Matsumoto H,Izuhara Y,Nagasaki T,Kanemitsu Y,Ishiyama Y,Morimoto C,Oguma T,Ito I,Muro S,Tabara Y,Matsuda F,Chin K,Hirai T
Organizer
American Thoracic Society International Conference 2018
Related Report
Int'l Joint Research
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[Presentation] Abnormality in Flow Volume Loop of Obstructive Index Reflects the Extent of Emphysema and Disease Severity in Obstructive Lung Diseases2018
Author(s)
Mochizuki F,Iijima H,Keiji F,Shimada T Watanabe A,Shiigai M,Ishikawa H,Kanazawa K,Yatagai Y,Masuko H,Sakamoto T,Oguma T,Sato S,Muro S,Hizawa N
Organizer
American Thoracic Society International Conference 2018
Related Report
Int'l Joint Research
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