Activation of PPARβ/δ Causes a Psoriasis-Like Skin Disease In Vivo
Figure 5
Congruent gene dysregulation in PPARβ/δ mice and psoriasis.
(a) Fold-change between the lesional skin of PPARβ/δ mice after administration of GW501516 and control mice (n = 3 per group), and between lesional and non-lesional skin samples from psoriasis obtained through the GAIN (I) and the GSE14905 (II) datasets, respectively, as detailed in Methods. Red: FC >1.5, Green: FC <0.8. Shown are the top 50 upregulated genes. The complete dataset is given in table S1. (b) Heat map showing all genes dysregulated in GW501516-fed PPARβ/δ mice (n = 1077), clustered by congruence with psoriasis. Color codes for –fold change are indicated. The genes in all clusters are detailed in table S2. (c) gene-set enrichment analysis (GSEA), performed using the top 500 genes upregulated in psoriasis lesions from the GSE14905 dataset (top), or the GAIN dataset (bottom), as genesets, respectively, and the complete mouse array collapsed to single genes as expression dataset. Analysis was run with 100 permutations and a classic statistic, NES = normalized enrichment score. The blue-red lines on the bottom represent heat-map of human genes found to be upregulated (blue on top) or downregulated in the mouse set. (d) Induction of cholesterol biosynthesis, conjugation, and channeling by PPARβ/δ. Red: upregulated in psoriasis and PPARβ/δ transgenic mice, blue: upregulated only in PPARβ/δ transgenic mice. Shaded boxes: repressed by Foxo1. (e) Induction of IL-1 signalling by PPARβ/δ. Datasets and color codes are as in (a). “n.s.”: p>0.01; “--”: fold change between 0.8–1.2., blue print: anti-inflammatory. * gene located within the IL1 cluster on chr. 2q between 113.2–113.7 Mb. (IL1F7 has only been identified in homo sapiens and bos taurus, the closest homologue in mice is IL1F5.).