The development of oligonucleotide therapeutics targeting epithelial cells in systemic sclerosis
| Project/Area Number |
16K15544
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Dermatology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Research Collaborator |
Trojanowska Maria
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 全身性強皮症 / 表皮細胞 / 線維化 / 外用薬 / マイクロニードル / IL-1 apha / アポトーシス / Fli1 / 皮膚免疫・炎症学 |
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| Outline of Final Research Achievements |
Based on the clinical observation that a part of patients with systemic sclerosis (SSc) develops skin sclerosis due to Koebner phenomenon, we investigated molecules invovled in this phenomenon and sought to develop a new treatment targeting such molecules against skin sclerosis of SSc. We identified IL-1 alpha and CTGF that are invovled in the epithelial cell-dependent induction of skin fibrosis in epithelial cell-specific Fli1 knockout mice (Fli1 flox/flox; K14-Cre) which spontaneously develop skin fibrosis. We also found the potential of epithelial cell-producing psoriasin and LL-37 to promote the development of skin fibrosis in the clinical studies with sera and skin sections of SSc patients. We are currently going to generate oligonucleotide therapeutics targeting these molecules produced by epithelial cells by using drug delivery system such as ointment, cream and microneedle.
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| Academic Significance and Societal Importance of the Research Achievements |
全身性強皮症(SSc)の主要3病態は免疫異常・炎症、血管障害、線維化であるため、これまで本症に対する新規薬剤の治療開発は免疫担当細胞、血管内皮細胞、線維芽細胞に対する作用に注目して進められてきた。本研究では、SScの線維化の病態に表皮細胞が関与していること、および表皮細胞がSScに対する新規治療薬開発の対象となりうる可能性を示した点に新規性があり、今後のSScに対する創薬を考えるうえで一石を投じる研究成果と言える。
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Report
(4 results)
Research Products
(9 results)
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[Journal Article] Systemic sclerosis complicated with localized scleroderma-like lesions induced by Koebner phenomenon.2018
Author(s)
Saigusa R, Asano Y, Yamashita T, Takahashi T, Nakamura K, Miura S, Ichimura Y, Toyama T, Taniguchi T, Sumida H, Tamaki Z, Miyazaki M, Yoshizaki A, Sato S.
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Journal Title
J Dermatol Sci.
Volume: 89
Issue: 3
Pages: 282-289
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Epithelial Fli1 deficiency drives systemic autoimmunity and fibrosis: Possible roles in scleroderma.2017
Author(s)
Takehiro Takahashi, Yoshihide Asano, Koji Sugawara, Kouki Nakamura, Takashi Yamashita, Ryosuke Saigusa, Yohei Ichimura, Tetsuo Toyama, Takashi Taniguchi, Kaname Akamata, Shinji Noda, Ayumi Yoshizaki, Daisuke Tsuruta, Maria Trojanowska, and Shinichi Sato
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Journal Title
Journal of Experimental Medicine
Volume: 214
Issue: 4
Pages: 1129-1151
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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