2003 Fiscal Year Final Research Report Summary
Pathophysiological analyses of molecules that are involved in damages of renal proximal tubular cells by proteinuria.
Project/Area Number |
14571023
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Kidney internal medicine
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Research Institution | Kobe Women's University (2003) Osaka University (2002) |
Principal Investigator |
TAKENAKA Masaru Kobe Women's University, Dept.of Home Economics, Professor, 家政学部, 教授 (20222101)
|
Co-Investigator(Kenkyū-buntansha) |
IMAI Enyu Osaka University, Department of Medicine, Associate Professor, 医学系研究科, 講師 (00223305)
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Project Period (FY) |
2002 – 2003
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Keywords | Progressive kidney disease / genes / oxidative stress / Proteinuria / Jak / Stat signal transduction / Glia maturation factor |
Research Abstract |
We found that brain specific protein, Glia maturation factor-b(GMF) was induced by proteinuria in renal proximal tubules. GMF was over-expressed in mouse renal proximal tubular cell lines(mProx24) NIH3T3 fibroblast cells. The over-expressed GMF caused changes of cell structure, accumulation of F-actin and apoptosis, revealing that its function was different from those reported in neural cells. It also demonstrated that the induction of GMF induced oxidative stress in the cells. We have constructed and reported gene expression profiles of normal and proteinuria disease model renal proximal tubules. The analyses of gene expression pattern revealed that there were a lot of genes induced by INF-γ. We hypothesized that proteinuria(mainly albumin) might stimulate cytokine signal transduction system. Overload of albumin in mProx24 cells activated Jak2, Stat1 and Stat5 but not Stat3 within 15 min. This activation of Jak/Stat system was inhibited by N-acetyl-L-cystein. Dye analyses showed that oxidative stress in cells was increased by albumin. These results suggested that oxidative stress generated by proteinuria was involved in the process of injuries of renal proximal cell.
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Research Products
(8 results)