Markers of psoriatic skin phenotype: androgen/estrogen and cortisone/cortisol imbalance, and DNA damage

Patients prone to psoriasis suffer after a breakdown of the epidermal barrier and develop poorly healing lesions with abnormal proliferation of keratinocytes. Strong inflammatory reactions with genotoxicity (short telomeres) suggest impaired immune defences with DNA damage repair response (DDR) in patients with psoriasis. Recent evidence indicates the existence of crosstalk mechanisms linking the DDR machinery and hormonal signalling pathways that cooperate to influence both progressions of many diseases and responses to treatment. The aim of this study was to clarify whether steroid biosynthesis and genomic stability markers are altered in parallel during the formation of psoriatic skin. Understanding between the interaction of the steroid pathway and DNA damage response is crucial to addressing underlying fundamental issues and managing resulting epidermal barrier disruption in psoriasis. Twenty patients with psoriasis and fifteen healthy volunteers were included in this study. Transcription levels of estrogen (ESR1, ESR2), androgen (AR), glucocorticoid/mineralocorticoid receptors (NR3C1, NR3C2), HSD11B1/HSD11B2 genes, and DNA damage sensors (SMC1A, TREX1, TREX2, SSBP3, RAD1, RAD18, EXO1, POLH, HUS1) were determined by Real-Time-PCR in blood and skin samples (Lesional, non-lesional) from psoriasis and control groups. ResultsWe found that ESR1, ESR2, HSD11B1, NR3C1, NR3C2, POLH, and SMC1A transcripts were significantly decreased and AR, TREX1, RAD1, and SSBP3 transcripts were increased dramatically in the lesional skin compared to skin samples of controls. As a result, we found that the regulation of the steroidogenic pathway was disrupted in the lesional tissue of psoriasis patients and that a sufficient glucocorticoid and mineralocorticoid response did not form and the estrogen/androgen balance was altered in favour of androgens. We suggest that an increased androgen response in the presence of DDR increases the risk of developing psoriasis. Although this situation may be the cause or the consequence of a disruption of the epidermal barrier, our data suggest developing new therapeutic strategies.