Characterization of the signaling pathway involved in the transcriptional regulation of semaphorin 3A in normal human epidermal keratinocytes

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19739
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Juntendo University
• Principal Investigator: KAMATA YAYOI 順天堂大学, 医学(系)研究科(研究院), 助教 (00410035)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 発現制御 / セマフォリン3A / 表皮角化細胞

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.

Free Research Field

皮膚科学