Ricerc@Sapienza

Psoriasis is a common, chronic, noncommunicable skin disease, with no clear cause or cure. Recent advances in psoriasis pathogenesis improved the understanding of disease mechanisms and resulted in the development of new immunobiologics and small molecules that help to control the chronic inflammation. However, long-term adverse effects of treatments and loss of drug efficacy are still major concerns for patients who need systemic therapy. During the last decade, the non-coding microRNAs (miRNAs) have emerged as key mediators of post-transcriptional gene silencing in several skin disorders, including psoriasis. In particular, several studies documented a differential expression of about a hundred of miRNAs in psoriatic skin compared with healthy skin, and the most highly changed miRNAs are related to inflammation and hyperproliferation pathways. However, the exact pathogenic roles of miRNAs have not been fully elucidated, and there is very little information regarding the genes involved in miRNAs biogenesis in psoriatic skin.Therefore, the present research proposal is aimed at investigating, on in vitro 2D and 3D psoriasis models, the expression of panel of selected miRNAs, their precursors, and the main protein-coding genes involved in miRNA processing and function. The latter will be also evaluated at the post-transcriptional and post-translational levels, by analyzing protein abundance, phosphorylation status (related to protein activity), and subcellular localization. We believe that the results obtainable with this work could fill important gaps on current knowledge about psoriasis, and represent a prerequisite for further preclinical research.