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Peritoneal membrane regeneration in peritoneal sclerosis

Research Project

Project/Area Number 16590789
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionNagasaki University

Principal Investigator

MIYAZAKI Masanobu  Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (10246100)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsperitoneal dialysis / peritoneal sclerosis / HSP47 / RNA interference / mesothelial cells / peritoneal regeneration
Research Abstract

The main pathological features of peritoneal membrane from the patients with long PD therapy are accumulation of collagen and loss of mesothelial cells. These peritoneal alteration leads peritoneal membrane failure and is the biggest problem disturbing the longer-PD treatment more than 5-7 years. To maintain the longer PD treatment, peritoneal regeneration is an important issue. In the present study, we focused two points. One is inhibition of peritoneal sclerosis progression and other is regeneration of mesothelial cells. In the former, we tried to silence the gene of an essential molecular chaperon associated with collagen synthesis, heat shock protein 47 (HSP47). In order to inhibition of HSP47 expression, we used small interfering RNA (siRNA) combined with cationized gelatin microspheres (CGM) as vector. After three days of single injection of HSP47 siRNA with CGM to parietal peritoneum, experimental peritoneal sclerosis was made by chlorhexidine injection into peritoneal cavity. H … More SP47 siRNA significantly inhibited the progression of peritoneal sclerosis. Furthremore, biodegradable CGM containing HSP47 siRNA could continuously release siRNA over 21 days as a result of microsphere degradation. In the experiment of peritoneal regeneration, we examined the peritoneum after the fibrotic parietal peritoneum was stripped from abdominal wall in rats with chlorhexidine-induced experimental peritoneal sclerosis. Seven days after the stripping procedure, the peritoneum was covered with cells positive for cytokeratins and HBME-1, markers for mesothelial cells. Scanning electron microscopy also showed microvilli at the surface of the cells, which were main morphological feature of peritoneal mesothelial cells. Immunochemical analysis demonstrated the appearance of cells positive for vimentin, a marker of mesenchymal cells before the regeneration of mesothelial cells. In conclusion, HSP47 gene silencing by siRNA method combined with CGM was effective for the inhibition of progression of experimental peritoneal sclerosis and mesothelial cells had possibility of regeneration even on the fibrotic peritoneum. Less

Report

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

    (18 results)

All 2005 2004

All Journal Article (18 results)

  • [Journal Article] Tissue-Specific Expression of Renin-Angiotensin System Components in IgA Nephropathy.2005

    • Author(s)
      Miyake-Ogawa C, Miyazaki M, Abe K, et al.
    • Journal Title

      Am J Nephrol. 25(1)

      Pages: 1-12

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Role of cyclophilin B in activation of interferon regulatory factor-3.2005

    • Author(s)
      Obata Y, Yamamoto K, Miyazaki M, et al.
    • Journal Title

      J Biol Chem 280(18)

      Pages: 18355-60

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Tissue-Specific Expression of Renin-Angiotensin System Components in IgA Nephropathy.2005

    • Author(s)
      Miyake-Ogawa C, Miyazaki M, Abe K, et al.
    • Journal Title

      Am J Nephrol. 7 ; 25(1)

      Pages: 1-12

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Role of cyclophilin B in activation of interferon regulatory factor-3.2005

    • Author(s)
      Obata Y, Yamamoto K, Miyazaki M, et al.
    • Journal Title

      J Biol Chem 6 ; 280(18)

      Pages: 18355-18360

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Role of cyclophilin B in activation of interferon regulatory factor-32005

    • Author(s)
      Obata Y, Yamamoto K, Miyazaki M, et al.
    • Journal Title

      J Biol Chem 280(18)

      Pages: 18355-18360

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Heat shock protein47 (HS47) siRNA ameliorates tubulointerstitial fibrosis in unilateral ureteral obstruction2005

    • Author(s)
      Miyazaki M, Abe K, Xia Z et al.
    • Journal Title

      Nephrology (Carlton) Suppl 10

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Aldosterone breakthrough during combined angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker in patients with IgA Nephropathy2005

    • Author(s)
      Horita Y, Tadokoro M, Miyazaki M et al.
    • Journal Title

      Nephrology(Carlton) Suppl 10

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Tissue-Specific Expression of Renin-Angiotensin System Components in IgA Nephropathy2005

    • Author(s)
      Miyake-Ogawa C, Miyazaki M, Abe K, et al.
    • Journal Title

      Am J Nephrol 25(1)

      Pages: 1-12

    • Related Report
      2004 Annual Research Report
  • [Journal Article] TNP-470, an angiogenesis inhibitor, suppresses the progression of peritoneal fibrosis in mouse experimental model.2004

    • Author(s)
      Yoshio Y, Miyazaki M, Abe K, et al.
    • Journal Title

      Kideney Int 66(4):

      Pages: 1677-85

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Renal synthesis of urokinase type-plasminogen activator, its receptor, and plasminogen activator inhibitor-1 in diabetic nephropathy in rats : Modulation by angiotensin-converting-enzyme inhibitor2004

    • Author(s)
      Miyazaki K, Miyazaki M, Koji T, et al.
    • Journal Title

      J Lab Clin Med 144(2)

      Pages: 69-77

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Pirfenidone attenuates expression of HSP47 in murine bleomycin-induced pulmonary fibrosis2004

    • Author(s)
      Kakugawa T, Mukae H, Hayashi T, Miyazaki, et al.M
    • Journal Title

      Eur Respir J 24(1)

      Pages: 57-65

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] TNP-470, an angiogenesis inhibitor, suppresses the progression of peritoneal fibrosis in mouse experimental model.2004

    • Author(s)
      Yoshio Y, Miyazaki M, Abe K, et al.
    • Journal Title

      Kidney Int. 66(4)

      Pages: 1677-1685

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Renal synthesis of urokinase type-plasminogen activator, its receptor, and plasminogen activator inhibitor-1 in diabetic nephropathy in rats : Modulation by angiotensin-converting-enzyme inhibitor.2004

    • Author(s)
      Miyazaki K, Miyazaki M, Koji T, et al.
    • Journal Title

      J Lab Clin Med 144(2)

      Pages: 69-77

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Pirfenidone attenuates expression of HSP47 in murine bleomycin-induced pulmonary fibrosis.2004

    • Author(s)
      Kakugawa T, Mukae H, Hayashi T, Miyazaki M, et al.
    • Journal Title

      Eur Respir J 24(1)

      Pages: 57-65

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Renal synthesis of urokinase type-plasminogen activator, its receptor, and plasminogen activator inhibitor-1 in diabetic nephropathy in rats.2004

    • Author(s)
      Miyazaki K, Miyazaki M, Koji T, et al.
    • Journal Title

      J Lab Clin Med. 144(2)

      Pages: 69-77

    • Related Report
      2004 Annual Research Report
  • [Journal Article] TNP-470, an angiogenesis inhibitor, suppresses the progression of peritoneal fibrosis in mouse experimental model2004

    • Author(s)
      Yoshio Y, Miyazaki M, Abe K, et al.
    • Journal Title

      Kidney Int 66(4)

      Pages: 1677-1685

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Pirfenidone attenuates expression of HSP47 in murine bleomycin-induced pulmonary fibrosis2004

    • Author(s)
      Kakugawa T, Mukae H, Hayashi T, Miyazaki M et al.
    • Journal Title

      Eur Respir J 24(1)

      Pages: 57-65

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of aldosterone synthase gene in IgA nephropathy (IgAN)2004

    • Author(s)
      Abe K, Miyazaki M, Kinoshita T, et al.
    • Journal Title

      Nephrology (Carlton) Supl 2

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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