| Budget Amount *help |
¥25,090,000 (Direct Cost: ¥19,300,000、Indirect Cost: ¥5,790,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2011: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
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| Outline of Final Research Achievements |
The present study examined a novel pathogenic mechanism of psoriasis where the epigenetic changes in affected keratinocytes promotes and stabilize the psoriatic skin lesions. The transcription activation cofactor LEDGF shows unique nuclear localization in the proliferating psoriatic keratinocytes. Our study revealed LEDGF shows extranuclear localization in G0/G1 keratinocyte cells, whereas upon stimulation with extracellular growth signals, it translocalizes to the nucleus via MEK and PI3K kinase-mediated mechanism. LEDGF was found to be a H3K36me3 reader, and when localized to the nucleus, it binds to the H3K36me3 motif and recruits the histone modification complex MLL. The present study is in support of the epigenetic model of psoriasis pathogenesis where the nuclear translocalized LEDGF enhances the di- and tri- methylation of H3K4 of the promoter regions of inflammatory cytokines and other psoriasis associated genes, leading to their enhanced and sustained expression.
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