223 Canonical and Dominant Negative Peroxisome Proliferator-Activated Receptor γ Isoforms are Differentially Expressed in Human Skin and Skin Appendages

Peroxisome proliferator-activated receptors (PPARs), which exert multiple key signaling functions in human skin physiology and pathology, exist various isoforms. These include canonical (cPPARγ1-4) dominant negative isoforms (dnPPARγ: γORF4 (γ1-3ORF4), truncated PPARG (PPARγtr) PPARγΔ5. Yet their exact expression patterns remain unclear. Therefore, we have localized quantified PPARγ biopsies from healthy donors by qRT-PCR or situ hybridization (for cPPARG). Protein was assessed using antibodies that detect all isoforms, cPPARγ, PPARγ2/γ2ORF4. Adipocytes express high levels of mRNA coding for cPPARG PPARGΔ5 PPARGtr, but minimal GORF4. Lower are also detected the sebaceous gland (SG), dermis, epidermis, listed order declining expression. cPPARG2/3/G2/3ORF4 found most prominently SGs while cPPARG1/4/G1ORF4 is comparable dermis SGs. PPARγtr higher as compared to epidermis. In hair follicle (HF), highest expressed isoform PPARGtr followed cPPARG1/3/4. cPPARγ transcripts mainly adipocytes, SGs, mesenchymal compartments rather than epidermis HF epithelium situ. This pattern confirmed at protein level with selected antibodies. Yet, PPARγ2/γ2ORF4 almost undetectable prominent bulge. Since show here dnPPARγ be differentially distributed within its appendages, topically systemically applied pharmacological modulators/agonists likely compartment-specific, receptor isoform-dependent clinical effects.