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The mechanisms involved in the regulation of mmesangial cell phenotype by endothetial cells : role of gap junction

Research Project

Project/Area Number 15590845
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionUniversity of Yamanashi

Principal Investigator

YAO Jian  University of Yamanashi, Department of Research Interdisciplinary Graduate School of Medicine and Engineering, Associate Professor, 大学院・医学工学総合研究部, 助教授 (50303128)

Co-Investigator(Kenkyū-buntansha) KITAMURA Masanori  University of Yamanashi, Department of Research Interdisciplinary Graduate School of Medicine and Engineering, Professor, 大学院・医学工学総合研究部, 教授 (90333062)
OITE Takashi  Niigata University, Graduate School of Medicine and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (60018744)
MORIOKA Tetsuo  Niigata University, Graduate School of Medicine and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (00210146)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsMesangial cells / Gap junction / Connexin43 / Endothelial cells / Nitric oxide / Phosphodiesterase 3 / Protein kinase A / Calcium / protein kinaseA / 糸球体
Research Abstract

One of intriguing features of mesangial cells (MCs) is their extraordinary abundance in gap junctions (GJs). However, information about the functional role of GJs in glomerular cells is still lacking. Our studies were designed to address this question. Our findings can be summarized as followings. 1. MCs are coupled by functional GJ channels. MCs were demonstrated to express GJ protein Cx43 and exhibited functional GJIC as assessed by dye-transfer assay. 2. GJ mediates the transmission of intercellular signal. Mechanical stimulation of a single MC initiated a rise in Ca^<2+> in the stimulated cells, which was followed by transmission of the signal to surrounding cells. The spreading of the Ca^<2+> signal in MCs was completely prevented by GJ inhibitors. 3. Regulation of MC phenotypes by glomerular endothelial cells via GJs. Using cultured human glomerular cells, endothelial cells were demonstrated to express GJ proteins including Cx43, Cx40 and Cx37, and GJ, which was functional, as as … More sessed by dye-transfer assay. Ultrastructural study revealed that presence of GJ protein Cx43 between endothelial cells and MCs. GJ might participates in the endothelial-mediated regulation of MC functions. 4. Regulation of GJ by endothelial-derived vasodilative factor nitric oxide (NO). Endothelial derived vasodiative factor, nitric oxide (NO), was identified to be a potent stimulator of Cx43 expression and functional gap junctional intercellular communication (GJIC) in MCs. This action of NO was shown to be due to the activation of protein kinase A via cGMP-dependent inhibition of phosphodiesterase 3 (PDE3). This finding may open a new window toward our further understanding of the vascular role of NO under various pathophysiologic situations. In conclusion, several lines of evidence support the important roles of GJs in MC functions. (1) MCs are extensively connected by functional GJs. (2) GJs in MCs participate in the regulation of important physiological processes, including tubuloglomerular feedback and glomerular filtration. (3) Factors critically involved in various processes of glomerular pathophysiology are potent regulators of Cx43 expression and GJIC in MCs. These data suggest that GJs may participate in glomerular pathophysiology. Less

Report

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

    (28 results)

All 2005 2004 2003 Other

All Journal Article (23 results) Publications (5 results)

  • [Journal Article] Nitric oxide-mediated regulation of connexin43 expression and gap junctional intercellular communication in mesangial cells2005

    • Author(s)
      Yao J
    • Journal Title

      J Am Soc Nephrol 16(1)

      Pages: 58-67

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Establishment of immortalized human glomerular endothelial cell lines and their application2005

    • Author(s)
      Harada T
    • Journal Title

      Nephron Exp Nephrol 99

      Pages: 38-45

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] A bioassay for fast, sensitive, and selective detection of halogenated and polycyclic aromatic hydrocarbons2005

    • Author(s)
      Kasai A
    • Journal Title

      Anal Biochem 337

      Pages: 84-88

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Nitric oxide-mediated regulation of connexin43 expression and gap junctional intercellular communication in mesangial cells.2005

    • Author(s)
      Yao J, Hiramatsu N, Zhu Y, Morioka T, Takeda M, et al.
    • Journal Title

      J Am Soc Nephrol 16

      Pages: 58-67

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Establishment of immortalized human glomerular endothelial cell lines and their application.2005

    • Author(s)
      Harada T, Batsford S, Morioka T, Yao J, Arakawa M, et al.
    • Journal Title

      Nephron Exp Nephrol 99

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Fast-track DRESSA : a bioassay for fast, sensitive, and selective detection of halogenated and polycyclic aromatic hydrocarbons.2005

    • Author(s)
      Kasai A, Hiramatsu N, Meng Y, Yao J, Maeda S, et al.
    • Journal Title

      Anal Biochem 337

      Pages: 84-88

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Fast-track DRESSA : a bioassay for fast, sensitive, and selective detection of halogenated and polycyclic aromatic hydrocarbons2005

    • Author(s)
      Kasai A
    • Journal Title

      Anal Biochem 337

      Pages: 84-88

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The characterization of a specific Thy-1 molecular epitope expressed on rat mesangial cells2004

    • Author(s)
      Morioka T
    • Journal Title

      Kidney Int 66(6)

      Pages: 2215-2223

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Real-time observation of glomerular hemodynamic changes in diabetic rats : effects of insulin and ARB2004

    • Author(s)
      Li B
    • Journal Title

      Kidney Int 66(5)

      Pages: 1939-1948

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] AP-1-independent sensitization to oxidative stress-induced apoptosis by proteasome inhibitors2004

    • Author(s)
      Hiramatsu N
    • Journal Title

      Biochem Biophys Res Commun 316

      Pages: 545-552

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Biosensing of dioxin and dioxin-like chemicals using secreted alkaline phosphatase2004

    • Author(s)
      Kasai A
    • Journal Title

      Anal Biochem 335

      Pages: 73-80

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The characterization of a specific Thy-1 molecular epitope expressed on rat mesangial cells.2004

    • Author(s)
      Morioka T, Yao J, Suzuki Y, Oite T
    • Journal Title

      Kidney Int 66

      Pages: 2214-2223

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Real-time observation of glomerular hemodynamic changes in diabetic rats : effects of insulin and ARB.2004

    • Author(s)
      Li B, Yao J, Kawamura K, Oyanagi-Tanaka Y, Hoshiyama M, et al.
    • Journal Title

      Kidney Int 66

      Pages: 1939-1948

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] AP-1-independent sensitization to oxidative stress-induced apoptosis by proteasome inhibitors.2004

    • Author(s)
      Hiramatsu N, Kasai A, Yao J, Meng Y, Takeda M, et al.
    • Journal Title

      Biochem Biophys Res Commun 316

      Pages: 545-552

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] DRESSA : biosensing of dioxin and dioxin-like chemicals using secreted alkaline phosphatase.2004

    • Author(s)
      Kasai A, Hiramatsu N, Meng Y, Yao J, Takeda M, et al.
    • Journal Title

      Anal Biochem 335

      Pages: 73-80

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Real-time observation of glomerular hemodynamic changes in diabetic rats: effects of insulin and ARB2004

    • Author(s)
      Li B
    • Journal Title

      Kidney Int 66(5)

      Pages: 1939-1948

    • Related Report
      2004 Annual Research Report
  • [Journal Article] DRESSA : biosensing of dioxin and dioxin-like chemicals using secreted alkaline phosphatase2004

    • Author(s)
      Kasai A
    • Journal Title

      Anal Biochem 335

      Pages: 73-80

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ATP-dependent mechanism for coordination of intercellular Ca2+ signaling and renin secretion in rat juxtaglomerular cells2003

    • Author(s)
      Yao J
    • Journal Title

      Circulation Research 93(4)

      Pages: 338-345

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Disturbance of syncytial cell function in glomerular mesangial cells involved in the progressive glomerular diseases2003

    • Author(s)
      Oite T
    • Journal Title

      Contrib Nephrol 139

      Pages: 12-19

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of high glucose on nitric oxide production and endothelial nitric oxide synthase protein expression in human glomerular endothelial cells.2003

    • Author(s)
      Hoshiyama M
    • Journal Title

      Nephron Exp Nephrol 95

      Pages: 62-68

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ATP-dependent mechanism for coordination of intercellular Ca2+ signaling and renin secretion in rat juxtaglomerular cells.2003

    • Author(s)
      Yao J, Suwa M, Li B, Kawamura K, Morioka T, et al.
    • Journal Title

      Circ Res 93

      Pages: 338-345

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Disturbance of syncytial cell function in glomerular mesangial cells involved in the progressive glomerular diseases.2003

    • Author(s)
      Oite T, Yao J, Morioka T
    • Journal Title

      Contrib Nephrol 139

      Pages: 12-19

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of high glucose on nitric oxide production and endothelial nitric oxide synthase protein expression in human glomerular endothelial cells.2003

    • Author(s)
      Hoshiyama M, Li B, Yao J, Harada T, Morioka T, et al.
    • Journal Title

      Nephron Exp Nephrol 95

      Pages: 62-68

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Yao J: "ATP-Dependent Mechanism for Coordination of Intercellular Ca2+ Signaling and Renin Secretion in Rat Juxtaglomerular Cells"Circulation Research. 93(4). 338-345 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hoshiyama M: "Effect of high glucose on nitric oxide production and endothelial nitric oxide synthase protein expression in human glomerular endothelial cells"Nephron. 95(2). 62-68 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Wu C: "Different expression patterns of Bcl-2, Bcl-xl, and Bax proteins after sublethal forebrain ischemia in C57Black/Crj6 mouse striatum"Stroke. 37(7). 1803-1808 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hiramatsu N: "AP-1-independent sensitization to oxidative stress-induced apoptosis by proteasome inhibitors"Biochemical and Biophysical Research Communications. 316. 545-552 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Xu Q: "Cellular defense against H202-induced apoptosis via MAP kinase-MKP-1 pathway"Free Radical Biology and Medicine. (In press). (2004)

    • Related Report
      2003 Annual Research Report

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

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