| Project/Area Number |
16K19739
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Dermatology
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| Research Institution | Juntendo University |
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Principal Investigator |
KAMATA YAYOI 順天堂大学, 医学(系)研究科(研究院), 助教 (00410035)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 発現制御 / セマフォリン3A / 表皮角化細胞 / 神経反発因子 / シグナル伝達 / アレルギー / アトピー性皮膚炎 / かゆみ |
|---|
| Outline of Final Research Achievements |
In this study, we investigated the signaling pathway involved in the transcriptional regulation of semaphorin 3A (Sema3A) in normal human epidermal keratinocytes (NHEK). The 5’-flanking region of Sema3A gene was cloned and a critical region for Sema3A promoter activity was identified. In this region, transcription factor binding sites including activator protein (AP)-1 were found. Chromatin immunoprecipitation assay revealed AP-1 bound to the proximal promoter. Up-regulation of Sema3A mRNA by calcium was significantly decreased by AP-1 inhibitor (T-5224). Similarly, it was also decreased by protein kinase C (PKC) α inhibitor (Go6976), MEK1/2 inhibitor (PD98059), and JNK inhibitor (SP600125). These results suggest that Sema3A expression in NHEK is mediated by the PKC/MAPK/AP-1 signaling axis in the proximal promoter, and provide a new insight to identify novel antipruritic drug targets.
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