TY - JOUR
T1 - Global gene expression analysis reveals evidence for decreased lipid biosynthesis and increased innate immunity in uninvolved psoriatic skin
AU - Gudjonsson, Johann E.
AU - Ding, Jun
AU - Li, Xing
AU - Nair, Rajan P.
AU - Tejasvi, Trilokraj
AU - Qin, Zhaohui S.
AU - Ghosh, Debashis
AU - Aphale, Abhishek
AU - Gumucio, Deborah L.
AU - Voorhees, John J.
AU - Abecasis, Goncalo R.
AU - Elder, James T.
N1 - Funding Information:
We express appreciation to all the research participants who participated in this study and to Lynda Hodges and Kathleen McCarthy. We thank Philip Stuart for statistical and technical assistance and Dr Anne Bowcock for providing gene lists referenced in Zhou et al., Physiol Genomics 13:69–78, 2003. This study was supported by grants to J.T.E. (National Institutes of Arthritis, Musculoskeletal and Skin Diseases, R01-AR054966) and J.E.G (American Skin Association, Dermatology Foundation).
PY - 2009
Y1 - 2009
N2 - Psoriasis is a genetically determined inflammatory skin disease. Although the transition from uninvolved into lesional skin is accompanied by changes in the expression of multiple genes, much less is known about the difference between uninvolved skin from psoriatic patients as opposed to skin from normal individuals. Multiple biochemical and morphological changes were reported decades ago in uninvolved psoriatic skin but remain poorly understood. Here, we show dysregulation of 223 transcripts representing 179 unique genes in uninvolved psoriatic skin, 178 of which were not previously known to be altered in their expression. The proteins encoded by these transcripts are involved in lipid metabolism, antimicrobial defenses, epidermal differentiation, and control of cutaneous vasculature. Cluster analysis of transcripts with significantly altered expression identified a group of genes involved in lipid metabolism with highly correlated gene expression. Promoter analysis showed enrichment for binding sites of three transcription factors; peroxisome proliferator-activator receptor alpha (PPARA), sterol regulatory element-binding protein (SREBF), and estrogen receptor 2 (ESR2), suggesting that the coordinate regulation of lipid metabolic genes may be related to the action of these factors. Taken together, our results identify a "pre-psoriatic" gene expression signature, suggesting decreased lipid biosynthesis and increased innate immunity in uninvolved psoriatic skin.
AB - Psoriasis is a genetically determined inflammatory skin disease. Although the transition from uninvolved into lesional skin is accompanied by changes in the expression of multiple genes, much less is known about the difference between uninvolved skin from psoriatic patients as opposed to skin from normal individuals. Multiple biochemical and morphological changes were reported decades ago in uninvolved psoriatic skin but remain poorly understood. Here, we show dysregulation of 223 transcripts representing 179 unique genes in uninvolved psoriatic skin, 178 of which were not previously known to be altered in their expression. The proteins encoded by these transcripts are involved in lipid metabolism, antimicrobial defenses, epidermal differentiation, and control of cutaneous vasculature. Cluster analysis of transcripts with significantly altered expression identified a group of genes involved in lipid metabolism with highly correlated gene expression. Promoter analysis showed enrichment for binding sites of three transcription factors; peroxisome proliferator-activator receptor alpha (PPARA), sterol regulatory element-binding protein (SREBF), and estrogen receptor 2 (ESR2), suggesting that the coordinate regulation of lipid metabolic genes may be related to the action of these factors. Taken together, our results identify a "pre-psoriatic" gene expression signature, suggesting decreased lipid biosynthesis and increased innate immunity in uninvolved psoriatic skin.
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U2 - 10.1038/jid.2009.173
DO - 10.1038/jid.2009.173
M3 - Article
C2 - 19571819
AN - SCOPUS:79959361260
SN - 0022-202X
VL - 129
SP - 2795
EP - 2804
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 12
ER -