Differantial Mechanism of Lung Cells induced by Mesenchymal Stem Cells and the Treatment of Intractable Respiratory Diseases
Project/Area Number |
15K09205
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
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Research Institution | Tohoku University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
Kanehira Masahiko 東北大学, 大学病院, 講師 (90374941)
Kikuchi Toshiaki 新潟大学, 大学病院, 教授 (10280926)
Irokawa Toshiya 東北大学, 事業支援機構, 准教授 (70375179)
Ogawa Hiromasa 東北大学, 事業支援機構, 准教授 (90361162)
Kurosawa Hajime 東北大学, 事業支援機構, 教授 (60333788)
Yamada Mitsuhiro 東北大学, 大学病院, 助教 (00396483)
Inoue Akira 東北大学, 大学病院, 教授 (70361087)
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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Keywords | 肺線維症 / 間葉系幹細胞 / エピジェネティクス / 酸化ストレス / ERストレス / 障害ストレス応答 / 成長因子 / 老化 / STC1 / SASP / マクロファージ / ミトコンドリア / エピゲノム / メタボローム |
Outline of Final Research Achievements |
We showed that stannniocalcin-1 (STC1) released from mesenchymal stem cells control the mitochondrial respiration and wound healing signals in alveolar macrophage and lung epithelial cells under oxidative and endoplasmic reticulum stresses. STC1 intra-tracheal injection ameliorate bleomycin induced pulmonary fibrosis in animal model. At this time, we report the metabolome analyses to elucidate the molecular mechanism of STC1 which ameliorate the fibrosis. The results showed that STC1 control the cysteine and methionine metabolism strongly. This pathway regulates the methylation and de-methyration of DNA and histone and the synthesis of DNA, reactive sulfur species (RSS) with redox activities, and manage the stress response of the organs. These things suggest new insights of pathology of pulmonary fibrosis to us.
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Peripheral alveolar nitric oxide concentration reflects alveolar inflammation in autoimmune pulmonary alveolar proteinosis.2018
Author(s)
Hirano T, Ohkouchi S, Tode N, Kobayashi M, Ono M, Satoh T, Mitsuishi Y, Watanabe A, Tabata M, Irokawa T, Ogawa H, Sugiura H, Kikuchi T, Akasaka K, Tazawa R, Inoue Y, Nakata K, Kurosawa H, Ichinose M.
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Journal Title
ERJ open research
Volume: 4
Issue: 1
Pages: 00071-2017
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Fractional Exhaled Nitric Oxide (FeNO) and Spirometry as INdicators of Inhalation Exposure to Chemical Agents in Pathology Workers2017
Author(s)
Ritsuko Arakawa Suzuki, Toshiya Irokawa, Hiromasa Ogawa, Shinya Ohkouchi, Masao Tabata, Susumu Togashi, Takeshi Nakamura, Noriko Ohisa, Etsuhiro Nikkuni, Emiri Miura, Kaoru Yoshida, Hioshi Inomata and Hajime Kurosawa
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Journal Title
Journal of Occupational and Environmental Medicine
Volume: in press
Issue: 5
Pages: 467-473
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Sequential GM-CSF Inhalation after Whole Lung Lavage for Pulmonary Alveolar Proteinosis: A Report of Five Intractable Cases.2017
Author(s)
Ohkouchi S, Akasaka K, Ichiwata T, Hisata S, Iijima H, Takada T, Tsukada H, Nakayama H, Machiya JI, Irokawa T, Ogawa H, Shibata Y, Ichinose M, Ebina M, Nukiwa T, Kurosawa H, Nakata K, Tazawa R
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Journal Title
Ann Am Thorac Soc.
Volume: 72
Issue: 8
Pages: 1074-1083
DOI
Related Report
Peer Reviewed
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[Journal Article] Exome sequencing deciphers a germline MET mutation in familial epidermal growth factor receptor-mutant lung cancer.2017
Author(s)
Tode N, Kikuchi T, Sakakibara T, Hirano T, Inoue A, Ohkouchi S, Tamada T, Okazaki T, Koarai A, Sugiura H, Niihori T, Aoki Y, Nakayama K, Matsumoto K, Matsubara Y, Yamamoto M, Watanabe A, Nukiwa T, Ichinose M.
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Journal Title
Cancer Sci
Volume: 印刷中
Issue: 6
Pages: 1263-1270
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Sequential GM-CSF inhalation after whole lung lavage for pulmonary alveolar proteinosis: a report of five intractable cases.2017
Author(s)
Ohkouchi S, Akasaka K, Ichiwata T, Hisata S, Iijima H, Takada T, Tsukada H, Nakayama H, Machiya J, Irokawa T, Ogawa H, Shibata Y, Ichinose M, Ebina M, Nukiwa T, Kurosawa H, Nakata K, Tazawa R.
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Journal Title
Ann Am Thorac Soc
Volume: 印刷中
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] A Semiquantitative CT Grading System for Evaluating Therapeutic Response in Pulmonary Alveolar Proteinosis2017
Author(s)
Sayoko Tokura, Masanori Akira, Tomohisa Okuma, Ryushi Tazawa, Toru Arai, Chikatoshi Sugimoto, Toshinori Takada, Koh Nakata, Haruyuki Ishii, Yasunori Kasahara, Masayuki Hojo, Shinya Ohkouchi, Yoshikazu Inoue
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Journal Title
Ann Am Thorac Soc
Volume: 印刷中
Related Report
Peer Reviewed
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[Journal Article] Peripheral Alveolar Nitric Oxide Concentration Reflects Macrophage Inflammation in Auto-Immune Pulmonary Alveolar Proteinosis2017
Author(s)
Taizou Hirano, Shinya Ohkouchi, Naoki Tode, Makoto Kobayashi, Manabu Ono, Teruyuki Satoh, Yoichiro Mitsuishi, Akira Watanabe, Masao Tabata, Toshiya Irokawa, Hiromasa Ogawa, Hisatoshi Sugiura, Toshiaki Kikuchi, Keiichi Akasaka, Ryushi Tazawa, Yoshikazu Inoue, Koh Nakata, Hajime Kurosawa and Masakazu Ichinose
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Journal Title
ERJ open research
Volume: 印刷中
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Mesenchymal stem cells attenuate ischemia-reperfusion injury after prolonged cold ischemia in a mouse model of lung transplantation: a preliminary study.2017
Author(s)
Watanabe T, Hoshikawa Y, Ishibashi N, Suzuki H, Notsuda H, Watanabe Y, Noda M, Kanehira M, Ohkouchi S, Kondo T, Okada Y.
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Journal Title
Surg Today
Volume: 47
Issue: 4
Pages: 425-425
DOI
Related Report
Peer Reviewed
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[Journal Article] Mesenchymal Stem Cells Correct Inappropriate Epithelial-mesenchyme Relation in Pulmonary Fibrosis Using Stanniocalcin-1.2015
Author(s)
Ono M, Ohkouchi S, Kanehira M, Tode N, Kobayashi M, Ebina M, Nukiwa T, Irokawa T, Ogawa H, Akaike T, Okada Y, Kurosawa H, Kikuchi T, Ichinose M.
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Journal Title
Mol Ther
Volume: 23
Issue: 3
Pages: 549-560
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Outcome of corticosteroid administration in autoimmune pulmonary alveolar proteinosis: a retrospective cohort study2015
Author(s)
Keiichi Akasaka, Takahiro Tanaka, Nobutaka Kitamura, Shinya Ohkouchi, Ryushi Tazawa, Toshinori Takada, Toshio Ichiwata, Etsuro Yamaguchi, Masaki Hirose, Toru Arai, Kentaro Nakano, Takahito Nei, Haruyuki Ishii, Tomohiro Handa, Yoshikazu Inoue and Koh Nakata
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Journal Title
BMC Pulmonary Medicine
Volume: 15
Issue: 1
Pages: 88-88
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] utcome of Corticosteroids Therapy in Autoimmune Pulmonary Alveolar Proteinosis2015
Author(s)
Keiichi Akasaka, Takahiro Tanaka, Keiko Shiiya, , Atsushi Hashimoto, Haruyuki Ishii, Shinya Ohkouchi, Ryushi Tazawa, Nobutaka Kitamura, Toshinori Takada, Koh Nakata
Organizer
ATS2015
Place of Presentation
United States of America(Denver)
Year and Date
2015-05-15
Related Report
Int'l Joint Research
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[Presentation] The Analysis Of Alveolar Macrophage Form On BALF Specimens In Secondary Pulmonary Alveolar Proteinosis2015
Author(s)
Haruyuki Ishii, , Ryushi Tazawa, Yoshikazu Inoue, Takeshi Saraya, Takashi Koide, Tomohiro Handa, Masato Morita, Shigeki Yamamoto, Yoshinori Tanino, Shinya Ohkouchi, Keisuke Tomii, Koh Nakata
Organizer
ATS2015
Place of Presentation
United States of America(Denver)
Year and Date
2015-05-15
Related Report
Int'l Joint Research
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[Presentation] A Mathematical Model that Estimates the Amount of Eliminated GM-CSF Autoantibody by Whole-Lung Lavage in Autoimmune Pulmonary Alveolar Proteinosis2015
Author(s)
Takahiro Tanaka, Keiichi Akasaka, Takashi Maruyama, Nobutaka Kitamura, , Atsushi Hashimoto, Keiko Shiiya, Yuuko Itoh, Shinya Ohkouchi, Ryushi Tazawa, Etsuro Yamaguchi, Toshio Ichiwata, Masaki Hirose, Toru Arai, Yoshikazu Inoue, Hirosuke Kobayashi, Koh Nakata
Organizer
ATS2015
Place of Presentation
United States of America(Denver)
Year and Date
2015-05-15
Related Report
Int'l Joint Research
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