期刊
SCIENTIFIC REPORTS
卷 7, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41598-017-18404-9
关键词
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资金
- National Psoriasis Foundation
- American Skin Association Carson Family Research Scholar Award in Psoriasis
- Babcock Foundation Endowment
- Murdough Family Center for Psoriasis
- Kenneth and Frances Eisenberg Emerging Scholar Award of the A. Alfred Taubman Medical Research Institute
- Doris Duke Charitable Foundation [2013106]
- National Institutes of Health: K08 grant [AR060802, R01 AR069071, P30 AR39750, R01 AR063437, R01 AR062546, R21 AR063852, K01 AR064765]
Keratinocyte (KC) hyper-proliferation and epidermal thickening are characteristic features of psoriasis lesions, but the specific contributions of KCs to plaque formation are not fully understood. This study used RNA-seq to investigate the transcriptome of primary monolayer KC cultures grown from lesional (PP) and non-lesional (PN) biopsies of psoriasis patients and control subjects (NN). Whole skin biopsies from the same subjects were evaluated concurrently. RNA-seq analysis of whole skin identified a larger number of psoriasis-increased differentially expressed genes (DEGs), but analysis of KC cultures identified more PP-and PN-decreased DEGs. These latter DEG sets overlapped more strongly with genes near loci identified by psoriasis genome-wide association studies and were enriched for genes associated with epidermal differentiation. Consistent with this, the frequency of AP-1 motifs was elevated in regions upstream of PN-KC-decreased DEGs. A subset of these genes belonged to the same co-expression module, mapped to the epidermal differentiation complex, and exhibited differentiation-dependent expression. These findings demonstrate a decreased differentiation gene signature in PP/PN-KCs that had not been identified by pre-genomic studies of patient-derived monolayers. This may reflect intrinsic defects limiting psoriatic KC differentiation capacity, which may contribute to compromised barrier function in normal-appearing uninvolved psoriatic skin.
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