Figure 1.
Back skin of mice after treatment with retinoid receptor-specific agonists and antagonists.
Representative photographs of dorsal skin areas from mice topically treated with vehicle control (acetone), or various retinoid receptor-selective agonists or antagonists for 14 days. Note the scaly skin of mice treated with the synthetic RXR agonist or the synthetic RARγ agonist, and appearing most pronounced in the RAR agonist (ATRA) treated group. 1all-trans retinoic acid/ATRA.
Figure 2.
H+E stained skin sections of mice after treatment with retinoid receptor-specific agonists and antagonists.
Representative photographs of H+E stained skin sections from mice topically treated with vehicle control (acetone), or various retinoid receptor-selective agonists or antagonists for 14 days. Note the epidermal thickness of mice treated with synthetic agonists for RXR or RARγ, and appearing most pronounced in the RAR agonist (ATRA) treated group. Epidermal thickness seemed comparable to vehicle control in mice treated with RARα agonist, RXR antagonist, RAR antagonist, and selective antagonists of RARα or RARγ. Original magnification (×20) was digitally magnified. 1all-trans retinoic acid/ATRA.
Figure 3.
Altered gene expression after treatment with retinoid receptor-specific agonists and antagonists.
Heat map displaying fold change of gene expression in mouse skin (n≥5/group) after treatment with retinoid receptor-specific agonists and antagonists compared to control mice (acetone). Genes are differentiated according to roles in retinoid metabolism or epidermal homeostasis. Retinoid target genes are further distinguished by specific function, i.e. retinoic acid synthesis (blue), retinoid transport (green), and genes unrelated to retinoid signaling (red). Color codes: dark red – significantly up-regulated; light red – non-significantly up-regulated; black – not regulated (±20%); light blue – non-significantly down-regulated; dark blue – significantly down-regulated. Statistical significance (p) is based on one-way ANOVA followed by Dunnett’s post test. A p-value <0.05 was considered significant. 1all-trans retinoic acid; 2also relevant as retinoid target gene.
Table 1.
Fold change of mRNA expression of genes involved in epidermal barrier homeostasis and chemotaxis in murine skin after two weeks of topical treatment with retinoid receptor-specific agonists or antagonists.
Table 2.
Fold change of retinoid metabolism-related gene expression in skin of mice after two weeks topical treatment with retinoid receptor-specific agonists.
Table 3.
Fold change of retinoid metabolism-related gene expression in skin of mice after two weeks topical treatment with retinoid receptor-specific antagonists.
Figure 4.
Retinoid receptor-selective gene regulation.
(a) Retinoid receptor-selective induction of genes with specific roles in retinoid signaling or epidermal barrier homeostasis in skin of mice treated topically with selective agonists for RARα, RARγ or RXR for 14 days. (b) Proposed outcome of selective signaling via RARα-RXR or RARγ-RXR in skin of mice induced by endogenous retinoids, such as all-trans retinoic acid.