| Project/Area Number |
21791520
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | Nagoya City University |
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Principal Investigator |
HIGASHIBATA Yuji 名古屋市立大学, 大学院・医学研究科, 研究員 (10381849)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 尿路結石 / オステオポンチン / 遺伝子組換えマウス / マトリクス / 分子標的治療 |
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| Research Abstract |
Osteopontin(OPN) has been described as playing a nonredundant role in renal crystal formation.(1) We investigated the effects of impaired domains of OPN, namely, the Arg-Gly-Asp(RGD) sequence and two calcium-binding sites on crystal formation. We used wild-type mice(WT group), OPN knockout mice(KO group), and OPN knockout mice carrying either a transgene in which the RGD sequence had been modified to Arg-Gly-Glu(RGE group) or whose two calcium-binding sites had been deleted(CaX group). In the WT group, crystal deposits increased gradually at the renal corticomedullary junction in an orderly fashion, whereas those in the KO group were observed sporadically in the renal cortex. In both the CaX and RGE groups, deposits were localized near the corticomedullary junction. Crystal deposition was greatest in the WT group and least in the KO group. The number of deposits in the RGE group was nearly equal to that in the KO group. The results indicated the possibility that each domain contributes to the mechanism by which OPN stimulates crystal formation.(2) We investigated the effects of an antimurine osteopontin antibody(35B6-Ab) that specifically reacts with the(162) SLAYGLR(168) sequence, which is exposed by thrombin cleavage and is located adjacent to the RGD sequence, on renal crystal formation. Scanning electron microscopy showed that the crystals in 35B6-Ab-treated mice were aberrantly formed and their density was low ; in contrast, the crystals in untreated mice that were not administered 35B6-Ab had a radial pattern of growth(rosette petal-like crystals), and their density was high. We conclude that thrombin-cleaved osteopontin plays an important role in formation of renal calcium crystals and that 35B6-Ab contributes to the remarkable inhibition of early-stage renal crystal formation by preventing renal tubular cell injury and crystal-cell attachment.
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