Abstract
In women, the flow of psoriasis is influenced by each phase of a woman’s life cycle. According to previous findings, significant changes in the levels of sex hormones affect the severity of the disease. Aim: The aim of this study was to identify the estrogen-responsive genes that could be responsible for the exacerbation of psoriasis in menopausal women. Methods: Skin samples of lesional skin donated by psoriasis patients (n = 5) were compared with skin samples of healthy volunteers (n = 5) using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The set of differentially expressed proteins was subjected to protein ontology analysis to identify differentially expressed estrogen-responsive proteins. The expression of discovered proteins was validated by qPCR and ELISA on four groups of female participants. The first group included ten psoriasis patients without menopause; the second included eleven postmenopausal patients; the third included five healthy volunteers without menopause; and the fourth included six postmenopausal volunteers. Moreover, the participants’ blood samples were used to assess the levels of estradiol, progesterone, and testosterone. Results: We found that the levels of estradiol and progesterone were significantly lower and the levels of testosterone were significantly higher in the blood of patients compared to the control. The protein ontology analysis of LC–MS/MS data identified six proteins, namely HMOX1, KRT19, LDHA, HSPD1, MAPK1, and CA2, differentially expressed in the lesional skin of female patients compared to male patients. ELISA and qPCR experiments confirmed differential expression of the named proteins and their mRNA. The genes encoding the named proteins were differentially expressed in patients compared to volunteers. However, KRT19 and LDHA were not differentially expressed when we compared patients with and without menopause. All genes, except MAPK1, were differentially expressed in patients with menopause compared to the volunteers with menopause. HMOX1, KRT19, HSPD1, and LDHA were differentially expressed in patients without menopause compared to the volunteers without menopause. However, no significant changes were found when we compared healthy volunteers with and without menopause. Conclusion: Our experiments discovered a differential expression of six estrogen-controlled genes in the skin of female patients. Identification of these genes and assessment of the changes in their expression provide insight into the biological effects of estrogen in lesional skin. The results of proteomic analysis are available via ProteomeXchange with identifier PXD021673.
Highlights
Psoriasis is an immune-mediated disease that is driven by Th1 and Th17 cells [1]
Skin biopsies for quantitative PCR (qPCR) and ELISA assays were obtained from female participants: 20 psoriasis patients and 11 healthy volunteers that we identified as qPCR/ELISA participants
Using independent methods of analysis, namely qPCR and ELISA (Figures 3 and 4), we examined their expression in menopausal and non-menopausal female patients and the respective groups of healthy volunteers (Figure 3A,D)
Summary
Psoriasis is an immune-mediated disease that is driven by Th1 and Th17 cells [1]. The incidence of psoriasis is similar in men and women. The mean age at onset of psoriasis presentation ranges between 15 and 20 years of age and the second peak occurs at the ages of 55–60 [2]. It is well-documented that the endogenous factors such as hormonal changes may trigger psoriasis [3]. The severity of psoriasis is influenced by each phase of a woman’s life cycle and the disease frequency tends to peak during puberty, postpartum, and menopause. The patients’ condition often improves during pregnancy [4]
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