|Tipo di tesi||Tesi di dottorato di ricerca|
|Titolo||Studio sull’influenza di MC1R sui differenti compartimenti cutanei: dal melanoma all’infiammazione, alle condizioni fisiologiche cutanee|
|Titolo in inglese||Study of MC1R influence on the different skin compartments: from melanoma to skin inflammation and physiologic conditions|
|Settore scientifico disciplinare||MED/35 - MALATTIE CUTANEE E VENEREE|
|Corso di studi||CLINICAL AND EXPERIMENTAL MEDICINE (CEM) - MEDICINA CLINICA E SPERIMENTALE|
|Data inizio appello||2019-03-21|
|Disponibilità||Accessibile via web (tutti i file della tesi sono accessibili)|
Il gene MC1R (melanocortin 1 receptor) codifica per un recettore il cui ligando principale è l’α-MSH (α-melanocyte-stimulating hormone). Il pathway α-MSH/MC1R è principalmente associato alla biosintesi di melanine e contribuisce alla riparazione del DNA.
The MC1R (melanocortin 1 receptor) gene codifies for a receptor, binding with high affinity α- melanocyte-stimulating hormone (α-MSH). α-MSH/MC1R pathway is mainly associated to melanin biosynthesis regulation and it contributes to DNA repair process. MC1R is highly polymorphic in Caucasians. Among these polymorphisms, some loss-of-functions variants have been associated with red hair, fair skin and freckles, thus being called RHC (red hair color) variants. Furthermore, a correlation of these variants with melanoma risk has been reported in different geographical areas. The objectives of this thesis are to explore the role of MC1R: 1. in melanoma, through statistical and molecular analysis, in terms of melanoma risk (independently from phenotypic characteristics) e in its metabolic reprogramming as well as in terms of response to anti-BRAF treatment in metastatic melanoma; 2. in skin phenotype of patients with skin inflammatory diseases (psoriasis), though a case-control study; 3. in physiologic skin conditions, analyzing different skin compartment by means of non-invasive imaging techniques (confocal microscopy and optical coherence tomography). Results obtained suggest that: 1. there is an association between MC1R polymorphisms and increased melanoma risk, independently on pigmentary traits; MC1R contributes to metabolic reprogramming in melanoma; MC1R is a clinical outcome marker in patients undergoing anti- BRAF treatment; 2. there is a significant association between psoriasis and wild-type MC1R, as compared to healthy control subjects; 3. MC1R status influences the variations of the composition of different skin compartments. In conclusion, these results provide new insights into the role of MC1R in different physio- pathologic conditions of the skin.