Journal of Investigative Dermatology

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Peroxisome-Proliferator-Activated Receptor (PPAR)-big gamma Activation Stimulates Keratinocyte Differentiation

Man Mao-Qiang, Ashley J Fowler, Matthias Schmuth, Peggy Lau, Sandra Chang, Barbara E Brown, Arthur H Moser, Liliane Michalik, Beatrice Desvergne, Walter Wahli, Mei Li, Daniel Metzger, Pierre H Chambon, Peter M Elias and Kenneth R Feingold

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Figure S1 (gif 114K)

Effects of PPAR-bold gamma activators on epidermal proliferation and apoptosis. Skin of mice was topically treated twice daily for 4 d with vehicle (propylene glycol: ethanol, 7:3, vol/vol) or with ciglitazone or troglitazone. Epidermal proliferation was measured by PCNA-staining (A) and apoptosis was assessed by TUNEL staining (B).

Figure S2 (gif 258K)

Effect of topical PPAR-bold gamma activators on epidermal differentiation. Skin of mice was topically treated twice daily for 4 d with vehicle (propylene glycol: ethanol, 7:3, vol/vol) or with the PPAR-gamma activators, ciglitazone or troglitazone. Involucrin and loricrin expression were assessed by immunohistochemistry (A). Filaggrin expression was assessed by in situ hybridization (B).

Figure S3 (gif 144K)

Effect of PPAR-bold gamma activators on cutaneous morphology in the TPA model of irritant contact dermatitis. Both inner and outer surface of both ears were topically treated with 10 muL of 0.03% phorbol 12-myristate-13-acetate (TPA). Forty-five minutes and 4 h after TPA application, 20 muL of test compounds were topically applied to both inner and outer surface of the left ear and the right ear was treated with acetone alone. The ear thickness was measured at 18 h following TPA application. Epidermal morphology was assessed by H&E staining.

Figure S4 (gif 110K)

Effect of PPAR-bold gamma activators on cutaneous morphology in the oxazolone model of allergic contact dermatitis. Both inner and outer surface of both ears were topically treated with 10 muL of 2% (wt/vol in acetone) oxazolone (4-ethoxymethylene-2-phenyl-2-oxazolin-5-one) 1 wk following primary sensitization with 20 muL of 15% oxazolone. Forty-five minutes and 4 h after application of 2% oxazolone, 10 muL of test compounds was topically applied to both inner and outer surface of the left ear, and the right ear was treated with acetone alone. The ear thickness was measured at 18 h following oxazolone application. Epidermal morphology was assessed by H&E staining.

Figure S5 (gif 196K)

Morphological changes in PPARbold gamma-deficient mice. Mouse skin from both wilditype and PPAR-gamma KO were obtained for paraffin sections. Both H&E staining (A) and PCNA staining (B) were used to analyze the morphological changes in PPAR-gamma KO and wild-type mice.

Figure S6 (gif 209K)

Effect of topical PPAR-bold gamma activators on epidermal differentiation in PPAR-bold gamma-deficient mice. Both wild-type and PPAR-gamma KO animals were topically treated with 40 muL of 10 mM ciglitazone in acetone for 4 d. A separate group of wild-type and PPAR-gamma KO animals were treated with vehicle alone for 4 d and served as controls. Skin biopsy was obtained for paraffin sections. Both filaggrin (A) and loricrin (B) staining were used to analyze epidermal differentiation.

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