| Project/Area Number |
21590169
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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 |
Medical pharmacy
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| Research Institution | Gifu Pharmaceutical University |
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Principal Investigator |
ADACHI Tetsuo 岐阜薬科大学, 薬学部, 教授 (40137063)
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| Co-Investigator(Kenkyū-buntansha) |
HARA Hirokazu 岐阜薬科大学, 薬学部, 准教授 (30305495)
KAMIYA Tetsuro 岐阜薬科大学, 薬学部, 助教 (60453057)
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| Co-Investigator(Renkei-kenkyūsha) |
IKEDA Tsunehiko 大阪医科大学, 医学部, 教授 (70222891)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 糖尿病網膜症 / 網膜血管内皮細胞 / 小胞体ストレス / レドクス恒常性 / 血管透過性 / タイトジャンクション / MAP kinase / NF-kB / extracellular-superoxide dismutase / MAP-kinase / デキサメタゾン / スーパーオキシドジスムターゼ / 酸化ストレス / 虚血 / EC-SOD / pericyte / 糖尿病性網膜症 / VEGF / オートクリン機構 |
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| Research Abstract |
Diabetic retinopathy(DR) is characterized by the development of intraretinal microvascular abnormalities. Endoplasmic reticulum(ER) stress is known to play a pathogenic role in vascular impairment in DR. Intravitreous injection of an ER stress inducer in mice increased the permeability of tracer dye across retinal blood vessels. The treatment of human retinal endothelial cells with ER stress inducers leads to the down-regulation of mainly claudin-5 among tight junction proteins, accompanied by elevation of retinal endothelial permeability. Moreover, p38 MAP kinase and subsequent NF-kB signaling pathways should contribute to the regulation of claudin-5 expression. The effects of dexamethasone are thought to be due to the transrepression of the above signaling and direct regulation of claudin-5 gene.
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