• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Based on the axis between macrophages and myofibroblasts, the organ-cross pathogenesis of incurable fibrosis

Research Project

Project/Area Number 26292152
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Veterinary medical science
Research InstitutionOsaka Prefecture University

Principal Investigator

Yamate Jyoji  大阪府立大学, 生命環境科学研究科, 教授 (50150115)

Co-Investigator(Kenkyū-buntansha) 竹中 重雄  大阪府立大学, 総合リハビリテーション学研究科, 教授 (10280067)
桑村 充  大阪府立大学, 生命環境科学研究科, 准教授 (20244668)
井澤 武史  大阪府立大学, 生命環境科学研究科, 准教授 (20580369)
秋吉 秀保  大阪府立大学, 生命環境科学研究科, 教授 (50420740)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2015: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords病理学 / 線維化 / マクロファージ / 筋線維芽細胞 / 肝線維化 / 腎線維化 / 皮膚線維化 / 臓器横断的 / 臓器横断的解析 / 上皮‐間葉転換 / 難治性疾患
Outline of Final Research Achievements

Macrophages appearing in experimentally-induced rat fibrosis of liver, kidney, pancreas, myocardium and skin could be evaluated based on M1/M2 macrophage polarization. There are some differences in macrophage appearance among organs. Basically, M1 macrophages appeared followed by M2 macrophages, in relation to increased cytokines by each type. M2 macrophages are related to development of myofibroblasts. Myofibroblasts showed cytoskeletons/proteins such as vimentin, desmin, alpha-smooth muscle action, grail fibrillary acidic protein, nestin and Thy-1 in various degrees. It was considered that the myofibroblasts might be derived from hepatic stellate cells, pancreatic stellate cells, pericytes, follicular mesenchymal stem cells and immature mesenchymal cells; renal myofibroblasts might be formed partly via epithelial-mesenchymal transition. Regulation of such macrophage appearance and myofibloblast development might become a possible therapeutic strategy for incurable fibrosis.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (39 results)

All 2018 2017 2016 2015 2014

All Journal Article (21 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 20 results,  Open Access: 21 results,  Acknowledgement Compliant: 9 results) Presentation (18 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results)

  • [Journal Article] Immunophenotypical analysis of pancreatic interstitial cells in the developing rat pancreas and myofibroblasts in the fibrotic pancreas in dogs and cats2017

    • Author(s)
      Hashimoto A, Karim MR, Izawa T, Kuwamura M, Yamate J.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 79 Issue: 12 Pages: 1920-1926

    • DOI

      10.1292/jvms.17-0423

    • NAID

      130006246746

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunolocalization of β-catenin, E-cadherin and N-cadherin in neonate and adult rat kidney2017

    • Author(s)
      Terada N, Karim MR, Izawa T, Kuwamura M, Yamate J.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 79 Issue: 11 Pages: 1785-1790

    • DOI

      10.1292/jvms.17-0439

    • NAID

      130006199252

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Participation of tumor-associated myeloid cells in progression of amelanotic melanoma (RMM Tumor Line) in F344 Rats, with particular reference to MHC Class II- and CD163-expressing cells.2017

    • Author(s)
      Bondoc A, Golbar HM, Pervin M, Katou-Ichikawa C, Tanaka M, Izawa T, Kuwamura M, Yamate J.
    • Journal Title

      Cancer Microenviron.

      Volume: 10 Issue: 1-3 Pages: 9-24

    • DOI

      10.1007/s12307-017-0193-x

    • Related Report
      2017 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Attenuation of thioacetamide-induced hepatocellular injury by short-term repeated injections associated with down-regulation of metabolic enzymes and relationship with MHC class II-presenting cells.2017

    • Author(s)
      Kuramochi M, Izawa T, Pervin M, Bondoc A, Kuwamura M, LaMarre J, Yamate J.
    • Journal Title

      Exp Toxicol Pathol.

      Volume: 69 Issue: 8 Pages: 589-597

    • DOI

      10.1016/j.etp.2017.05.005

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characterization of pancreatic islet cell tumors and renal tumors induced by a combined treatment of streptozotocin and nicotinamide in male SD rats.2017

    • Author(s)
      Kato Y, Masuno K, Fujisawa K, Tsuchiya N, Torii M, Hishikawa A, Izawa T, Kuwamura M, Yamate J.
    • Journal Title

      Exp Toxicol Pathol.

      Volume: 69 Issue: 7 Pages: 413-423

    • DOI

      10.1016/j.etp.2017.03.007

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Attenuation of alpha-naphthylisothiocyanate (ANIT)-induced biliary fibrosis by depletion of hepatic macrophages in rats.2017

    • Author(s)
      Golbar HM, Izawa T, Bondoc A, Wijesundera KK, Tennakoon AH, Kuwamura M, Yamate J.
    • Journal Title

      Exp Toxicol Pathol.

      Volume: 69 Issue: 4 Pages: 221-230

    • DOI

      10.1016/j.etp.2017.01.005

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reference control data obtained from an in vivo comet-micronucleus combination assay using Sprague Dawley rats.2017

    • Author(s)
      Kasamoto S, Masumori S, Tanaka J, Ueda M, Fukumuro M, Nagai M, Yamate J, Hayashi M.
    • Journal Title

      Exp Toxicol Pathol.

      Volume: 69 Issue: 4 Pages: 187-191

    • DOI

      10.1016/j.etp.2017.01.002

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Histopathological Analysis of Rat Hepatotoxicity Based on Macrophage Functions: in Particular, an Analysis for Thioacetamide-induced Hepatic Lesions2016

    • Author(s)
      Yamate J, Izawa T, Kuwamura M.
    • Journal Title

      Food Safety

      Volume: 4 Issue: 3 Pages: 61-73

    • DOI

      10.14252/foodsafetyfscj.2016012

    • NAID

      130005267072

    • ISSN
      2187-8404
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The kinetics of damage-associated molecular patterns (DAMPs) and Toll-like receptors during thioacetamide-induced acute liver injury in rats.2016

    • Author(s)
      Kuramochi M, Izawa T, Pervin M, Bondoc A, Kuwamura M, Yamate J.
    • Journal Title

      Exp Toxicol Pathol .

      Volume: 68 Issue: 8 Pages: 471-477

    • DOI

      10.1016/j.etp.2016.06.005

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] M1-/M2-macrophage polarization in pseudolobules consisting of adipohilin-rich hepatocytes in thioacetamide (TAA)-induced rat hepatic cirrhosis.2016

    • Author(s)
      Wijesundera KK, Izawa T, Tennakoon AH, Golbar HM, Tanaka M, Kuwamura M, Yamate J.
    • Journal Title

      Exp Mole Pathol

      Volume: 101 Issue: 1 Pages: 133-142

    • DOI

      10.1016/j.yexmp.2016.07.005

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Immunophenotypical characterization and influence on liver homeostasis of depleting and repopulating hepatic macrophages in rats injected with clodronate.2016

    • Author(s)
      Pervin M, Golbar HM, Bondoc A, Izawa T, Kuwamura M, Yamate J.
    • Journal Title

      Exp Toxicol Pathol.

      Volume: 68 Issue: 2-3 Pages: 113-124

    • DOI

      10.1016/j.etp.2015.11.003

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Transient effects of empty liposomes on hepatic macrophage populations in rats2016

    • Author(s)
      Pervin M, Golbar HM, Bondoc A, Izawa T, Kuwamura M, Yamate J.
    • Journal Title

      Journal of Toxicologic Pathology

      Volume: 29 Issue: 2 Pages: 139-144

    • DOI

      10.1293/tox.2015-0082

    • NAID

      130005151011

    • ISSN
      0914-9198, 1881-915X
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Depletion of hepatic macrophages aggravates liver lesions induced in rats by thioacetamide (TAA).2016

    • Author(s)
      Golbar HM, Izawa T, Wijesundera KK, Bondoc A, Tennakoon AH, Kuwamura M, Yamate J.
    • Journal Title

      Toxicol Pathol.

      Volume: 44 Issue: 2 Pages: 246-258

    • DOI

      10.1177/0192623315621191

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Analysis of glial fibrillary acidic protein (GFAP)-expressing ductular cells in a rat liver cirrhosis model induced by repeated injections of thioacetamide (TAA)2015

    • Author(s)
      Tennakoon, A. H. Izawa, T. Wijesundera, K. K. Katou-Ichikawa, C. Tanaka, M. Golbar, H. M. Kuwamura, M. Yamate, J.
    • Journal Title

      Experimental and Molecular Pathology

      Volume: 98 Issue: 3 Pages: 476-485

    • DOI

      10.1016/j.yexmp.2015.03.010

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Pathogenesis of type 2 epithelial to mesenchymal transition (EMT) in renal and hepatic fibrosis.2015

    • Author(s)
      Tennakoon AH, Izawa T, Kuwamura M, Yamate J.
    • Journal Title

      Journal of Clinical Medicine (Review)

      Volume: 5 Issue: 1 Pages: 1-16

    • DOI

      10.3390/jcm5010004

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] M1-/M2-macrophages contribute to the development of glutathione S-transferase placental form (GST-P)-positive pseudolobules in thioacetamide-induced rat cirrhosis.2015

    • Author(s)
      Wijesundera KK, IzawaT, TennakoonAH, Murakami H, Golbar HM, Katou-Ichikawa C, Tanakawa M, Kuwamura M, Yamate J.
    • Journal Title

      Experimental and Toxicologic Pathology

      Volume: 67 Issue: 9 Pages: 467-475

    • DOI

      10.1016/j.etp.2015.05.002

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] M1- and M2-macrophage polarization in thioacetamide (TAA)-induced rat liver lesions; a possible analysis for hepato-pathology2014

    • Author(s)
      Wijesundera KK, Izawa T, Murakami H, Tennakoon AH, Golbar HM, Katou-Ichikawa C, Tanaka M, Kuwamura M, Yamate J
    • Journal Title

      Histology and Histopathology

      Volume: 29 Pages: 497-511

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] M1- and M2-macrophage polarization in rat liver cirrhosis induced by thioacetamide (TAA), focusing on Iba1 and galectin-32014

    • Author(s)
      Wijesundera KK, Izawa T, Tennakoon AH, Murakami H, Golbar HM, Kato-Ichikawa C, Tanaka M, Kuwamura M, Yamate J
    • Journal Title

      Exp Mol Pathol

      Volume: in press Issue: 3 Pages: 382-392

    • DOI

      10.1016/j.yexmp.2014.04.003

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nestin expression in remodeling of α-naphthylisothiocyanate (ANIT)-induced acute bile duct injury in rats2014

    • Author(s)
      Golbar HM, Izawa T, Wijesundera KK, Tennakoon AH, Katou-Ichikawa C, Tanaka M, Kuwamura M, Yamate J
    • Journal Title

      Journal of Comparative Pathology

      Volume: 151 Issue: 2-3 Pages: 255-263

    • DOI

      10.1016/j.jcpa.2014.05.003

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of neutrophil gelatinase-associated lipocalin and osteopontin in renal tubular regeneration and interstitial fibrosis after cisplatin-induced renal failure2014

    • Author(s)
      Kashiwagi E, Tonomura Y, Kondo C, Masuno K, Fujisawa K, Tsuchiya N, Matsushima S, Torii M, Takasu N, Izawa T, Kuwamura M, Yamate J
    • Journal Title

      Experimental and Toxicologic Pathology

      Volume: 66 Issue: 7 Pages: 301-311

    • DOI

      10.1016/j.etp.2014.04.007

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Calponin Expression in Renal Tubulointerstitial Fibrosis Induced in Rats by Cisplatin2014

    • Author(s)
      Yuasa, T., Yano, R., Izawa, T., Kuwamura, M., Yamate, J
    • Journal Title

      Journal of Toxicologic Pathology

      Volume: 27 Issue: 1 Pages: 97-103

    • DOI

      10.1293/tox.2013-0048

    • NAID

      130003391344

    • ISSN
      0914-9198, 1881-915X
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Time dependent cytoprotective phenomenon of lipopolysaccharide in TAA-induced acute liver injury in rats2018

    • Author(s)
      Karim MR,Pervin M,倉持瑞樹,井澤武史,桑村 充,山手丈至.
    • Organizer
      第34回日本毒性病理学会学術集会(沖縄県那覇市).2018年1月25日・;26日.
    • Related Report
      2017 Annual Research Report
  • [Presentation] 炎症誘導因子(DAMPs)と関連シグ;ナルを介したチオアセトアミト(TAA)誘発ラット急性 肝障害における進展機序の解析.2018

    • Author(s)
      倉持瑞樹,井澤武史,Pervin M,Karim MR,桑村 充,山手丈至.
    • Organizer
      第34回日本毒性病理学会学術集会(沖縄県那覇市).2018年1月25日・26日.
    • Related Report
      2017 Annual Research Report
  • [Presentation] トリメチルスス誘発神経毒性ラットモデル;ルにおける血清 miRNA バイオマーカー探索.2017

    • Author(s)
      緒方敬子,武田周二,串田昌彦,桑村 充,井澤武史,山手丈至.
    • Organizer
      第33回日本毒性病理学会学術集会
    • Place of Presentation
      堺市
    • Year and Date
      2017-01-26
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] デキストラン硫酸ナトリウム(DSS)誘発ラット結腸病変における体性幹細胞認識抗体A3 陽性細胞の動態.2017

    • Author(s)
      仁科嘉修,市川(加藤)智彩,倉持瑞樹,井澤武史,桑村 充,山手丈至.
    • Organizer
      第33回日本毒性病理学会学術集会
    • Place of Presentation
      堺市
    • Year and Date
      2017-01-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] Effect of lipopolysaccaride on autophagy and autophagic response in liver homeostasis in rats.2017

    • Author(s)
      Karim MR,Pervin M,井澤武史,桑村 充,山手丈至.
    • Organizer
      第33回日本毒性病理学会学術集会
    • Place of Presentation
      堺市
    • Year and Date
      2017-01-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] チオアセトアミド反復投与ラット肝障害モデルにおける肝細胞傷害の軽減効果の解析.2017

    • Author(s)
      倉持瑞樹,井澤武史,Pervin M,Karim MR,Bondoc A,桑村 充,山手丈至.
    • Organizer
      第33回日本毒性病理学会学術集会
    • Place of Presentation
      堺市
    • Year and Date
      2017-01-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] M1/M2分極化に基づいたイソプロテレノール誘発ラット心筋傷害におけるマクロファージの特性解析.2017

    • Author(s)
      古賀真昭,Karim MR,倉持瑞樹,井澤武史,桑村 充,山手丈至.
    • Organizer
      第33回日本毒性病理学会学術集会
    • Place of Presentation
      堺市
    • Year and Date
      2017-01-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] ブチル二塩化スズ誘発ラット膵線維化におけるマクロファージ;と間葉系細胞の動態.2017

    • Author(s)
      橋本 愛,Bondoc A,Karim MR,井澤武史,桑村 充,山手丈至.
    • Organizer
      第33回日本毒性病理学会学術集会
    • Place of Presentation
      堺市
    • Year and Date
      2017-01-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] 線維化病態モニターマウスを用いた腎障害モデルの病態解析.2017

    • Author(s)
      山口達弘,加藤祐樹,奥田智彦,山手丈至.
    • Organizer
      第33回日本毒性病理学会学術集会
    • Place of Presentation
      堺市
    • Year and Date
      2017-01-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] 1.Damage-Associated Molecular Patterns (DAMPs) and MHC class II-expressing Cells in Thioacetamide (TAA)-Induced Rat Liver Injury.2017

    • Author(s)
      Kuramochi M, Izawa T, Pervin M, Bondoc A, Karim MR, Kuwamura M, Yamate J.
    • Organizer
      STP (Society of Toxicologic Pathology) 36th Annual Symposium (Montreal, Canada). 24th-29th, June, 2017.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Lipopolysaccharide-mediated autophagy protects against thioacetamide-induced acute liver injury in rats.2017

    • Author(s)
      2.Karim MR, Pervin M, Kuramochi M, Izawa T, Kuwamura M, Yamate J.
    • Organizer
      STP (Society of Toxicologic Pathology) 36th Annual Symposium (Montreal, Canada). 24th-29th, June, 2017.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腸管の発生と線維化における幹細胞認識抗体(A3)標識細胞の動態.2016

    • Author(s)
      仁科嘉修,市川(加藤)智彩,倉持瑞樹,井澤武史,桑村 充,山手丈至.
    • Organizer
      第159回日本獣医学会学術集会
    • Place of Presentation
      藤沢市
    • Year and Date
      2016-09-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] チオアセトアミド誘発ラット肝障害における障害誘導因子とMHCクラスII発現細胞の特性.2016

    • Author(s)
      倉持瑞樹,井澤武史,Pervin M,Bondoc A,桑村 充,山手丈至.
    • Organizer
      第32回日本毒性病理学会学術集会
    • Place of Presentation
      サンアポート高松・かがわ国際会議場(香川県高松)
    • Year and Date
      2016-01-28
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 2.Pathogenic Role and Regulation of Galectin-3 Expression in Renal Fibrosis and TGF-beta 1 Induced Fibrogenesis.2015

    • Author(s)
      Juniantito V, Izawa T, Kuwamura M, Priosoeryanto BP, Harlina E, Yamate J
    • Organizer
      ACVP/ASVCP/STP Combined Annual Meeting.
    • Place of Presentation
      Minneapolis Convention Center (Minneapolis, USA)
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マクロファージと毒性病理学2015

    • Author(s)
      山手丈至
    • Organizer
      第31回日本毒性病理学会学術集会
    • Place of Presentation
      タワーホール船堀、東京
    • Year and Date
      2015-01-29 – 2015-01-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Analyses of hepatic macrophages depleted by clodoronate in rat liver.2014

    • Author(s)
      M. Pervin, H. M. Golbar, B. Alexandra, K. K. Wijesundera, T. Izawa, M. Kuwamura, and J. Yamate
    • Organizer
      The American College of Veterinary Pathologists (ACVP)
    • Place of Presentation
      Atlanta, GA, USA.
    • Year and Date
      2014-11-09 – 2014-11-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Characterization of repopulating macrophages in liver after depletion with liposomal clodronate in rats.2014

    • Author(s)
      M. Pervin, H. M. Golbar, B. Alexandra, M. Uemura, T. Izawa, M. Kuwamura and J. Yamate
    • Organizer
      第157回日本獣医学会学術集会
    • Place of Presentation
      北海道大学、札幌
    • Year and Date
      2014-09-09 – 2014-09-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Macrophage-derived galectin-3 is the key regulator of acute hepatic fibrogenesis in rats.2014

    • Author(s)
      H. M. Golbar, T. Izawa, B. Alexandra, K. K. Wijesundera, A. H. Tennakoon, C. Katou-Ichikawa, M. Tanaka, M. Kuwamura and J. Yamate
    • Organizer
      The 33rd Annual Symposium of the Society of Toxicologic Pathology (STP)
    • Place of Presentation
      Washingon DC, USA.
    • Year and Date
      2014-06-22 – 2014-06-26
    • Related Report
      2014 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2019-03-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi