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Clarification of multi-functions of macrophage populations in renal fibrosis and therapeutic strategies

Research Project

Project/Area Number 15380217
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Clinical veterinary science
Research InstitutionOsaka Prefecture University

Principal Investigator

YAMATE Jyoji  Osaka Prefecture University, Life and Environmental Sciences, Associate Professor, 生命環境科学研究科, 助教授 (50150115)

Co-Investigator(Kenkyū-buntansha) KUWAMURA Mitsuru  Osaka Prefecture University, Life and Environmental Sciences, Assistant Professor, 生命環境科学研究科, 講師 (20244668)
TSUKAMOTO Yasuhiro  Osaka Prefecture University, Life and Environmental Sciences, Associate Professor, 生命環境科学研究科, 助教授 (90305657)
KUMAGAI Daijirou  Osaka Prefecture University, Life and Environmental Sciences, Research Assistant, 生命環境科学研究科, 助手 (70316016)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥9,900,000 (Direct Cost: ¥9,900,000)
Fiscal Year 2005: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2003: ¥4,000,000 (Direct Cost: ¥4,000,000)
Keywordsrenal fibrosis / macrophage / myofibroblast / fibrogenic factor / cisplatin / dexamethasone / hepatic fibrosis / rat model / LPS / エナラプリル / タウリン / 浸潤マクロファージ / 固着マクロファージ / 樹状細胞 / 免疫組織化学 / 病理発生
Research Abstract

The purposes of this study were to clarify the functional roles of macrophages appearing in the renal fibrosis, and to explore the useful therapeutic strategies for the intractable diseases, on the basis of the data.
Dexamethasone (DX), an anti-inflammatory drug, was injected in rat models of chronic renal fibrosis induced by cisplatin. As a result, the DX injection decreased the number of ED1-positive exudate macrophages, leading to the reduction of the progressive renal fibrosis. However, the appearance of ED2-positive resident macrophages and OX6-positive antigen presenting macrophages were not influenced by the DX injection. In addition, the concomitant addition of TGF-β1 (a fibrogenic factor) and DX to rat renal interstitial cells (NRK-49F) and rat undifferentiated mesenchymal cells (MT-9) decreased the number of cells reacting to α-smooth muscle actin (α-SMA). These findings of in vivo and in vitro studies indicate that DX ameliorates the progressive renal fibrosis through the dec … More reased number of ED1-positive macrophages and the reduction of the formation of α-SMA-positive myofibroblastic cells induced by TGF-β1. Using acute rat renal fibrosis model, the effect of dietary azuki bean (Vigna angularis) was investigated as a result, the administration with azuki bean dramatically decreased the number of ED1-positive macrophages, and reduced the renal fibrosis. It is shown nutritionally that the azuki bean may contain a substance which is able to reduce the renal fibrosis.
Using rat hepatic fibrosis model induced by thioacetoamide, of which the pathogenesis is similar to that of renal fibrosis, the influence of GdCl_3, an inhibitor of Kupffer cell functions, was investigated. As a result, the treatment with GdCl_3 reduced the number of different macrophage populations, and in particular, fibrosis around the periportal areas was improved. These data shout be referred to the understanding of the pathogenesis of renal fibrosis.
The present studies clarified some functions of macrophage populations appearing in renal fibrosis, and provided some useful therapeutic methods which may be used in human medicine, though at experimental levels. Less

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (25 results)

All 2005 2004 Other

All Journal Article (22 results) Publications (3 results)

  • [Journal Article] Protective effect o dietary azuki bean (Vigna angularis) seed coats against renal interstitial fibrosis of rats induced by cisplatin2005

    • Author(s)
      Sato S., et al.
    • Journal Title

      Nutrition 21・4

      Pages: 504-511

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Nephrotoxicity of a novel antineoplastic platinum complex, nedaplatin : a comparative study with cisplatin in rats2005

    • Author(s)
      Uehara T., et al.
    • Journal Title

      Arch.Toxicol. 79・8

      Pages: 451-460

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Cisplatin-induced renal interstitial fibrosis in neonatal rats, developing as solitary nephron unit lesions2005

    • Author(s)
      Yamate J., et al.
    • Journal Title

      Toxicol.Pathol. 133・2/3

      Pages: 92-102

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effects o gadolinium chloride s on the appearance of macrophage populations and fibrogenesis in thioacetamide-induced rat hepatic lesions2005

    • Author(s)
      Ide M., et al.
    • Journal Title

      J.Comp.Pathol. 133・2/3

      Pages: 92-102

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Protective effect of polyphenol-containing azuki bean (Vignaangularis) seed coats on the renal cortex in streptozotocin-induced diabetic rats2005

    • Author(s)
      Sato S., et al.
    • Journal Title

      J.Nutr.Biochem. 16・9

      Pages: 547-553

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differential immunoexpressions of cytoskeletons in renal epithelial and interstitial cells in rat and canine fibrotic kidneys, and in kidney-related cell lines under fibroeenic stimuli2005

    • Author(s)
      Yamate J., et al.
    • Journal Title

      Exp.Toxicol.Pathol. 57・2

      Pages: 135-147

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Protective effect of dietary azuki bean (Vigna angularis) seed coats against renal interstitial fibrosis of rats induced by cisplatin.2005

    • Author(s)
      Sato S., et al.
    • Journal Title

      Nutrition 21(4)

      Pages: 504-511

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Nephrotoxicity of a novel antineoplastic platinum complex, nedaplatin : a comparative study with cisplatin in rats.2005

    • Author(s)
      Uehara T., et al.
    • Journal Title

      Arch.Toxicol. 79(8)

      Pages: 451-460

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cisplatin-induced renal interstitial. fibrosis in neonatal rats, developing as solitary nephron unit lesions.2005

    • Author(s)
      Yamate J., et al.
    • Journal Title

      Toxicol.Pathol. 3(2)

      Pages: 207-217

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effects of gadolinium chloride (GdCl_3) on the appearance of macrophage populations and fibrogenesis in thioacetamide-induced rat hepatic lesions.2005

    • Author(s)
      Ide M., et al.
    • Journal Title

      J.Comp.Pathol. 133(2/3)

      Pages: 92-102

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Protective effect of polyphenol-containing azuki bean (Vigna angularis) seed coats on the renal cortex in streptozotocin-induced diabetic rats.2005

    • Author(s)
      Sato S., et al.
    • Journal Title

      J.Nutr.Biochem. 16(9)

      Pages: 547-553

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differential immunoexpressions of cytoskeletons in renal epithelial and interstitial cells in rat and canine fibrotic kidneys, and in kidney-related cell lines under fibrogenic stimuli.2005

    • Author(s)
      Yamate J., et al.
    • Journal Title

      Exp.Toxicol.Pathol. 57(2)

      Pages: 135-147

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Protective effect of dietary azuki bean (Vigna angularis) seed coats against renal interstitial fibrosis of rats induced by cisplatin2005

    • Author(s)
      Sato S., et al.
    • Journal Title

      Nutrition 21・4

      Pages: 504-511

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cisplatin-induced renal interstitial fibrosis in neonatal rats, developing as solitary nephron unit lesions2005

    • Author(s)
      Yamate J., at al.
    • Journal Title

      Toxicol.Pathol. 33・2

      Pages: 207-217

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effects of gadolinium chloride (GdCl_3) on the appearance of macrophage populations and fibrogenesis in thioacetamide-induced rat hepatic lesions2005

    • Author(s)
      Ide M., at al.
    • Journal Title

      J.Comp.Pathol 133・2/3

      Pages: 92-102

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Protective effect of polyphenol-containing azuki bean (Vigna angularis) seed coats on the renal cortex in streptozotocin-induced diabetic rats2005

    • Author(s)
      Sato S., e t al.
    • Journal Title

      J.Nutr.Biochem. 16・9

      Pages: 547-553

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Differential immunoexpressions of cytoskeletons in renal epithelial and interstitial cells in rat and canine fibrotic kidneys, and in kidney-related cell lines under fibrogenic stimuli2005

    • Author(s)
      Yamate J., at al.
    • Journal Title

      Exp.Toxicol.Pathol. 57・2

      Pages: 135-147

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effects of lipopolysaccharide on the appearance of macrophage populations and fibrogenesis in cisplatin-induced rat renal injury2004

    • Author(s)
      Yamate J., et al.
    • Journal Title

      Exp Toxicol Pathol 56

      Pages: 13-24

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Immunohistochemical detection of macrophage populations in the short-finned pilot whale (Globicephala macrorhychus) and Risso's dolphin (Grampus griseus)2004

    • Author(s)
      Kawashima M., et al.
    • Journal Title

      J Comp Pathol 130

      Pages: 32-40

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Distributive and phagocytic characteristics of hepatic macrophages in five cetaceans belonging to delphinidae and ziphiidae2004

    • Author(s)
      Kawashima M., et al.
    • Journal Title

      J Vet Med Sci 66

      Pages: 671-680

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Immunophenotypical changes of myofibroblasts appearing in thioacetamide-induced hepatic fibrosis in rats2004

    • Author(s)
      Ide M., et al.
    • Journal Title

      J Toxicol Pathol 17

      Pages: 231-238

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Morphologic characteristics of pulmonary macrophages in cetaceans : particular reference to pulmonary intravascular macrophages as a newly identified type2004

    • Author(s)
      Kawashima M., et al.
    • Journal Title

      Vet Pathol 41

      Pages: 682-686

    • Related Report
      2004 Annual Research Report
  • [Publications] Ide, M., et al.: "Emergence of different macrophage populations in hepatic fibrosis following thioacetoamide-induced acute heatocyte injury in rats."J.Comp.Pathol.. 128(1). 41-51 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawashima, M., et al.: "Immunohistochemical detection of macrophages in the Short-finned pilot whale and Risso's dolphin."J.Comp.Pathol.. 130(1). 32-40 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 山手 丈至: "慢性腎疾患-腎線維化の進展機序-(腎疾患の新たな診断と治療法を目指して)"獣医畜産新報. 57(1). 616-626 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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