On 12 November at 14:00 Helen Vaher will defend her doctoral thesis “MicroRNAs in the regulation keratinocyte responses in psoriasis vulgaris and atopic dermatitis” for obtaining the degree of Doctor of Philosophy (in Medicine).
Professor Ana Rebane, University of Tartu
Professor Külli Kingo, University of Tartu
Professor Charlotte Menne Bonefeld, University of Copenhagen (Denmark)
The skin is the largest organ in our body that protects us from the outside environment. Dysfunction in the interaction and protective functions of the skin cells can lead to the development of various inflammatory skin diseases. Psoriasis and atopic dermatitis are among the most common chronic inflammatory skin diseases. The incidence of psoriasis is on average 2-3% and in atopic dermatitis 2-5% in adults and even up to 20% in children. Psoriasis is characterized by a red inflammatory rash with scaly patches. Atopic dermatitis is characterized by an inflammatory itchy rash. Patients with these diseases have a reduced quality of life and also have several co-morbidities, such as psoriatic arthritis, cardiovascular disease, and mental health problems. The development of both diseases involves the skin cells that are capable of producing signaling molecules that affect the movement and activity of immune cells in the skin, and immune cells in turn affect skin cells. The result is a clinical phenotype seen in psoriasis and atopic dermatitis.
miRNAs are short RNA molecules that regulate the expression of a very large number of genes in cells. In this thesis, the functions of miR-146a and miR-146b (miR-146a / b) and miR-10a in skin cells in relation to psoriasis or atopic dermatitis, respectively, were described. MiR-146a has previously been shown to be able to suppress inflammatory processes in the skin, but the role of miR-146b and miR-10a in skin cells was unknown. We found that the levels of miR-146a/b in the skin of patients with psoriasis were increased and suppressed the levels of genes that in turn affect inflammatory processes and the division of skin cells. We have shown that miR-146a/b inhibits the cellular processes characteristic to psoriasis, however, the higher expression of miR-146a/b in the skin of psoriasis patients is not able to prevent the development of the disease. Secondly, we detected elevated levels of miR-10a in the skin of atopic dermatitis patients. We found that the level of miR-10a in skin cells depends on the stage of cell differentiation and that the main role of miR-10a is to slow down the division of skin cells and, also, to suppress inflammatory processes in skin cells. Therefore, it can be hypothesized that miR-10a affects the development and course of atopic dermatitis.