| Project/Area Number |
18K09450
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56060:Ophthalmology-related
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| Research Institution | Kurume University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
石川 桂二郎 九州大学, 医学研究院, 助教 (00795304)
園田 康平 九州大学, 医学研究院, 教授 (10294943)
池田 康博 九州大学, 医学研究院, 准教授 (20380389)
久冨 智朗 九州大学, 医学研究院, 准教授 (50404033)
中尾 新太郎 九州大学, 医学研究院, 講師 (50583027)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 糖尿病網膜症 / テネイシンC / ペリオスチン / 分子標的 / ファイブロネクチン / 3次元構造解析 / 線維血管増殖 / 質量分析 / テネイシン / 増殖組織 |
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| Outline of Final Research Achievements |
We found significant correlation between concentrations of PN, TNC and FN in PDR vitreous humor. Interleukin-13 (IL-13) promoted mRNA and protein expression of PN and TNC in human microvascular endothelial cells (HRECs). IL-13 promoted angiogenic functions of HRECs. Single inhibition of PN or TNC and their dual inhibition by siRNA suppressed the up-regulated angiogenic functions. Pathological pre-retinal neovessels of oxygen-induced retinopathy (OIR) mice were attenuated in PN knock-out, TNC knock-out and dual knock-out mice compared to wild-type mice. Both in vitro and in vivo, PN inhibition had a stronger inhibitory effect on angiogenesis compared to TNC inhibition, and had a similar effect to dual inhibition of PN and TNC. Furthermore, PN knock-out mice showed scant TNC expression in pre-retinal neovessels of OIR retinas. Our findings suggest that interaction of PN and TNC facilitates pre-retinal angiogenesis, and PN is an effective therapeutic target for PDR.
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| Academic Significance and Societal Importance of the Research Achievements |
我々は、極小検体である増殖組織のゲノムワイド遺伝子発現解析に初めて成功した。引き続いて、抽出された増殖組織特徴的遺伝子群であるペリオスチン・テネイシンCが眼内増殖組織促進に極めて重要な役割を果たすことを明らかにした今回、ペリオスチン・テネイシンC蛋白複合体の抑制にペリオスチン抑制のみで十分効果的であることがわかった。ペリオスチン、テネイシンCの網膜での発現レベルは低く、ペリオスチンを標的とした分子標的薬を創製できれば、正常網膜にほとんど障害を与えることなく、増殖組織のみを消退させる治療となることが期待される。
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