| Project/Area Number |
21K08307
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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 53050:Dermatology-related
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 全身性強皮症 / 線維化 / piRNA |
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| Outline of Research at the Start |
研究代表者は本研究計画において、①piRNAの皮膚線維化への関与、②血清中濃度の診断・病勢マーカーとしての有用性、そして③piRNAによるマウス皮膚線維化の抑制効果の3点を明らかにしたい。
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| Outline of Final Research Achievements |
No difference was found in the PIWIL1-4 levels between normal and cultured scleroderma dermal fibroblasts. Among piRNAs predicted to target scleroderma-related molecules, we first found significant piR-32364 up-regulation in scleroderma dermal fibroblasts, likely due to intrinsic TGF-β signaling. Forced piR-32364 overexpression in normal fibroblasts significantly reduced COL1A1 expression both at mRNA and protein levels, but not COL1A2. Thus, piR-32364 overexpression in scleroderma fibroblasts may be the negative feedback against collagen up-regulation, which could suggest the potential of piRNAs as a therapeutic target.
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| Academic Significance and Societal Importance of the Research Achievements |
研究の創造性として、病態の解明のみならず、診断・治療の面で臨床医学への波及効果を有する。具体例を挙げると、皮膚組織や血清で特異的piRNAを検出する事で皮膚線維化の定量評価ができれば、RNAが蛋白の上流に存在し一般に刺激に対し迅速に反応する事を考えると、より鋭敏な全く新しいマーカーの開発につながる。さらに皮膚においてpiRNAを特異的に補充あるいは阻害する事で線維化を抑制することができれば、特異的で侵襲や副作用の少ない全く新しい予防法・治療薬の開発につなげることができる。
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