Development of an in vitro pigmented human skin model for studies of hyper- and hypopigmenting substances and melanogenesis-related pathways.

• Grant number: 23/12768-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: January 01, 2024
• End date: July 31, 2025
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Silvya Stuchi Maria-Engler
• Grantee: Gabriella Lisboa dos Santos
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Melanogenesis is a complex and multifactorial process that is determinant for the safety of the skin against solar radiation. Inside melanocytes, the epidermal cells responsible for the melanin synthesis, melanossomes do the process with the transcription of key enzymes by the microphtalmia-associated transcription factor, conversion of L-tyrosine in dopaquinone by tyrosinase and subsequent transformations by the tyrosinase-related protein 1and tautomerase dopachrome. Thus, the two existing subtypes of melanin are formed: eumelanin and pheomelanin. Either extrinsic factors, as UV radiation, or intrinsic ones, as the expression of the basic fibroblast growth factor, are involved in the melanogenesis. Thus, several genetic and acquired disorders that modify genes involved in the process can cause hyperpigmentation or hypopigmentation. Nowadays, there are two major drivers of the research in this field: the big market demand for specific substances that can act in the melanogenesis and the worldwide prohibitions of cosmetic tests on animals. Therefore, the aim of this project is to construct an in vitro pigmented dermal-epidermal model as a platform for safety and efficacy testing of products. To this end, the constructs will be tested regarding their behavior against UV radiation and the activities of two standard compounds, forskolin and tranexamic acid, which acts in different stages of melanogenesis, in order to contribute to the study of molecular parameters of this pathwaty.