| Project/Area Number |
19K08788
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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 | Asahi University (2022-2023)
Gifu University (2019-2021) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
水谷 陽子 岐阜大学, 医学部附属病院, 講師 (60759950)
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| Project Period (FY) |
2019-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | プログラニュリン / 乾癬 / アトピー性皮膚炎 / サイトカイン / progranulin / 炎症性皮膚疾患 |
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| Outline of Research at the Start |
プログラニュリン（PGRN）は表皮細胞で発現し、特に乾癬表皮で発現が増加しているが、その意義は不明である。本研究では重要な炎症性皮膚疾患である乾癬およびアトピー性皮膚炎について、患者血清中のPGRN濃度測定、皮疹組織におけるPGRNの発現、培養表皮細胞を用いてPGRNのサイトカイン産生に対する作用を検討する。また、これらの疾患のモデルマウスを作成し、血清中、皮疹の組織中のPGRN濃度を測定する。本研究は乾癬とアトピー性皮膚炎の病態におけるPGRNの役割を明らかにするとともにPGRN及びそのアナログであるAtsttrinを用いた新規治療の開発に寄与すると考えられる。
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| Outline of Final Research Achievements |
Serum PGRN (progranulin) concentrations were significantly increased in psoriasis compared to healthy subjects and were positively correlated with PASI (psoriasis area and severity index) score, a clinical marker of psoriasis. We also found a correlation with serum PGRN concentrations and serum IL-17 and IL-22 concentrations. PGRN concentrations were significantly higher in sera from patients with atopic dermatitis and correlated positively with TARC (thymus and activation-regulated chemokine) and IL-36γ concentrations.
The effects of PGRN on cultured epidermal cells were examined: IL-23 expression in epidermal cells was increased when PGRN was added to the culture medium. Furthermore, the expression of PGRN was significantly increased by the addition of IL-22, IL-36γ, and TNF-α to the culture medium. These results suggest that PGRN plays a role in the pathogenesis of psoriasis and atopic dermatitis via cytokines.
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| Academic Significance and Societal Importance of the Research Achievements |
プログラニュリンはサイトカイン産生を介して乾癬、アトピー性皮膚炎などの皮膚疾患の病態形成に関与することが明らかになり、今後の病態解明と創薬に役立つと考えられる。
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