Egy magreceptor, a peroxisoma proliferátor aktivált receptor (PPAR) patogenetikai szerepe psoriasisban és UV indukálta nonmelanoma bőrdaganatokban = The role of peroxisome proliferator activated receptor (PPAR), a nuclear receptor, in the pathomechanism of psoriasis and UV induced non-melanoma skin cancers

A peroxisoma proliferator aktivalt receptor (PPAR alfa, beta es gamma) ligand altal aktivalt transzkripcios faktorok, magreceptorok. Lipid ligandjaik altal a kornyezeti hatasok kozvetlenul szabalyozzak a DNS-ben hordozott genetikai informaciok atirasat es befolyasoljak a proliferaciot, a differenciaciot, a sejthalalt, az egyedfejlődest es a homeosztazist. Bőrbetegsegek (psoriasis, bőrdaganatok, acne) patomechnaizmusa tanulmanyozasara alkalmas modell a megfelelő sejtek in vitro tenyeszete, valamint bőrbiopszias mintak feldolgozasa. In vitro keratinocyta (KC) differenciacio soran genexpresszios vizsgalatokkal uj, differenciacioban szerepet jatszo geneket identifikaltunk. KC tenyeszetben UVB besugarzas utan meghataroztuk QRT-PCR-hez az optimalis normalizalo geneket. Tovabba kimutattuk, hogy mindharom PPAR mRNS differenciaciotol fuggően expresszalodik, UVB-re szintjuk csokken. Faggyumirigyben a PPAR gamma expresszioja es szignalizacioja kulonbozik patologias, normal es tenyesztett faggyumirigyben. Kisszamu acnes beteg PPAR gamma gen DNS szekvenciajaban nem talaltunk elterest. Az epidermalis KC-k lipid anyagcserejeben fontos ABC molekulacsalad nehany tagjanak mRNS szintje UVB besugarzas hatasara csokkent, mig egy splice varians novekedett. KC-kban viralis RNS-t imitalo hatasra az innate immunrendszerhez tartozo Nod-like receptorok expresszioja valtozik. Mindezen adatok hozzajarulnak a gyulladasos es proliferativ bőrbetegsegek patomechanizmusanak jobb megertesehez. | PPAR alpha, -beta and -gamma which are transcription factors activated by ligands. Through their lipid ligands environmental effects regulate directly the transcription of the genetic information coded in DNA, and influence the proliferation, differentiation, cell death, embryogenesis and homeostasis. In vitro cell culture, assessment of skin biopsy samples are suitable models for studying pathomechanism of skin diseases. We identified new genes relevant for differentiation using gene expression analysis of keratinocytes (KC) differentiated in vitro. We identified in KC culture the optimal normalizer genes for QRT-PCR after UVB irradiation. We show, that the mRNA expression of the 3 PPAR studied is dependent on the differentiation state of the cells and decreases after UVB. In sebaceous gland the expression, signalization of PPAR-gamma were shown to be different in pathologic, normal, cultured sebaceous gland. Studying some acne patients we could not observe any alteration in their PPAR-gamma gene DNA sequence. mRNA expression of some members of ABC molecule family important in the lipid metabolism of epidermal KC was decreased after UVB irradiation, whereas the mRNA expression of a splice variant was increased. In KC the expression of the Nod-like receptors belonging to the innate immune system was increased after viral RNA mimicking stimulus. All these data contribute to the better understanding of the pathomechanism of inflammatory and proliferative skin diseases.