Roles of vitamin D in the progression of renal interstitial fibrosis
| Project/Area Number |
17590838
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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 |
Kidney internal medicine
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| Research Institution | Osaka City University |
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Principal Investigator |
SHIOI Atsushi Osaka City University, Graduate School of Medicine, Lecturer (90260801)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIMURA Eiji Osaka City University, Graduate School of Medicine, Associate Professor (20145775)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,610,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | vitamin D / renal interstiatial fibrosis / a-smooth muscle actin / E-cadherin / klotho / vitamin D receptor / unilateral ureteral obstruction / nephrotoxic serum nephritis / α-smmoth muscle actin / siRNA / Wntシグナル / マクロファージ / 半月体形成性腎炎 |
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| Research Abstract |
Transforming growth factor-β (TGF-β) inhibited expression of E-cadherin mRNA and increased expression of α-smooth muscle actin (α-SMA) in NRK-52E cells. 1 α,25-Dihydroxyvitamin D_3 (1,25(OH)_2D_3) partially antagonized the effects of TGF-β on expression of E-cadherin and α-SMA in NRK-52E cells. In NRK-52E cells overexpressing human vitamin D receptor (VDR) gene, 1,25 (OH)_2D_3 did not attenuate the effects of TGF-β on E-cadherin expression, while it significantly amplified its effects on α-SMA expression.
TGF-β reduced expression of E-cadherin and klotho mRNAs in HK-2 cells. On the other hand, 1,25 (OH)_2D_3 not only increased E-cadherin and klotho expression, but also partially antagonized the inhibitory effects of TGF-β on E-cadherin and klotho expression. Moreover, small interfering RNA of klotho significantly amplified the inhibitory effects of TGF-β on E-cadherin expression in HK-2 cells.
In the unilateral ureteral obstruction models, interstitial infiltration of macrophages and deposition of collagen were increased in VDR knock-out mice compared .with wild type mice. Furthermore, in the renal fibrosis models induced by nephrotoxic serum nephritis, VDR-deficient mice showed severe interstitial fibrosis compared with wild type mice.
These results suggest that vitamin D may play the protective roles in the progression of renal interstitial fibrosis.
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Report
(4 results)
Research Products
(36 results)
