| Project/Area Number |
16591616
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | JICHI MEDICAL UNIVERSITY |
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Principal Investigator |
YAGISAWA Takashi Jichi Medical University, School of Medicine, Professor, 医学部, 教授 (80167692)
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| Co-Investigator(Kenkyū-buntansha) |
YASHI Masahiro Jichi Medical University, School of Medicine, Instructor, 医学部, 助手 (70348019)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | polycystic kidney disease / epithelium / stone formation / chloride channel / NADC-1 / citrate / CFTR / 尿細管上皮細胞 / NaDC-1 |
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| Research Abstract |
We investigated the development of cyst and stone formation and the effect of citrate on these processes, focusing on changes in chloride channel-K(CLC-K), NaDC-1 and osteopontin in an experimental model for renal cysts.
The following results were obtained :
1.The expression of CLC-K decreased in the process of cyst formation, which suggests that CLC-K is a significant factor in the development of polycystic kidney disease (PKD).
2.Citrate increased the expression of CLC-K in the epithelia, resulting in retardation of cyst formation.
3.Significant hypocitraturia was observed and the expression of NaDC-1 moved to the apical site of the epithelia in PKD.
4.Stone formation occurred more rapidly and widely in PKD than in controls by using ethylene glycol.
5.Osteopontin (OPN) expression increased in the PKD.
6.Citrate decreased OPN expression and improved hypocitraturia, resulting in suppression of stone formation.
These results suggest that intra-cystic/tubular fluid accumulation by transepithelial chloride secretion involving CLC-K is an important step in cyst formation. Stone formation easily complicates due to hypocitraturia and the increase of OPN expression in PKD. Cyst formation associated with the decrease of CLC-K expression is suppressed by citrate. Citrate also retards stone formation by improving hypocitraturia and decreasing OPN expression in PKD.
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