Differential Expression of Estrogen-Responsive Genes in Women with Psoriasis

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.

Proteomic Studies of Psoriasis

“…A detailed study of disease-associated proteins revealed 123 DEPs in lesional and normal-looking skin of female patients. Contrarily, their expression did not significantly change in similar samples of male patients [48]. The following ontology analysis discovered 14 overrepresented biological processes.…”

“…The signs  and  indicate that the protein expression is increased and decreased, respectively. The sign  indicates that chemical reaction between HCO3 − and can be reversed [48].…”

“…Although Zhou et al [41], reported many proteins already recognized by the others, they also discovered some DEPs, namely OAS2, IFIT3, IRF3, and MeCP2, that were not previously associated with psoriasis. Analyzing the expression of OAS2 in patients' skin and blood, the authors discovered its strong correlations with PASI − and can be reversed [48].…”

“…The regulation of estrogen-responsive proteins in lesional skin of female psoriasis patients.The signs  and  indicate that the protein expression is increased and decreased, respectively. The sign  indicates that chemical reaction between HCO3 − and can be reversed[48].…”

Personalized Medicine in the Field of Inflammatory Skin Disorders

“…Sobolev et al found a differential expression of six estrogen-controlled genes (HMOX1, KRT19, LDHA, HSPD1, MAPK1, and CA2) in the skin of female patients with psoriasis compared to male patients with psoriasis and concluded that these proteins may be involved in the defense of skin cells against inflammation damage. Considering that estrogens exert anti-inflammatory effects, low estrogen levels can influence the course of the disease in women with psoriasis [ 6 ]. Using a mouse model of induced psoriatic dermatitis, Surcel et al obtained promising results after the administration of IgY, which led to the improvement in skin lesions and the normalization of immune parameters.…”