| Project/Area Number |
10044252
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Experimental pathology
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| Research Institution | Niigata University |
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Principal Investigator |
KAWACHI Hiroshi School of Medicine, Associate Professor, 医学部, 助教授 (60242400)
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| Co-Investigator(Kenkyū-buntansha) |
SHIA Michael A. Boston Univ., Medical Center, Associate Professor, 医学部, 助教授
SALANT David J. Boston Univ., Medical Center, Professor, 医学部, 教授
SHIMIZU Fujio School of Medicine, Professor, 医学部, 教授 (40012728)
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| Project Period (FY) |
1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | glomerulus / epithelial cell / slit diaphragm / tight junction / p51 / ZO-1 / proteinuria |
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| Research Abstract |
The aim of our project is to elucidate the structure and the function of slit diaphragm, which locates between adjacent foot processes of glomerular epithelial cells. All molecules, which are identified to be a component of slit diaphragm, are ZO-1 and p51. ZO-1 was originally reported to be a component of tight junction. P51 is a target molecule of proteinuria inducing- monoclonal antibody (mAb) 5-1-6, which our group established. We have already demonstrated that p51 and ZO-1 lie close to each other on opposite sides of the podocyte plasma membrane at the point of insertion of the slit diaphragm. We also showed that the amounts of ZO-1 and p51 were decreased and they were redistributed coincident with the development of proteinuria induced by mAb 5-1-6. Thus, we hypothesized that a molecular interaction between p51 and ZO-1 contributes to the normal glomerular permeability barrier. To analyze the mechanism of the redistributions of ZO-1 and p51, we tested the sensitivity of these redistributions to some drugs. We found that the they were redistributed by Ca^<++> calmoduli-cytoskelton and actin-dependent, and tubulin-independent manner. We concluded that proteinuria resulted from the dysfunction of slit diaphragm caused by redistributions of p51 and ZO-1. We reported these findings at the 31st annual meeting of American Society of Nephrology in 1998 (J Am Soc Nephrol 9, 499, 1998 abstract).
We found that metanephric culture cells expressed p51. We are trying the cloning of p51 using cDNA library of mRNA from the metanephric culture with our colleagues of Boston University.
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