Sobolev Vladimir, Soboleva Anna, Denisova Elena, Denieva Malika, Dvoryankova Eugenia, Suleymanov Elkhan, Zhukova Olga V, Potekaev Nikolay, Korsunskaya Irina, Mezentsev Alexandre
Centre of Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Russian Academy of Sciences, 119334 Moscow, Russia.
Scientific Research Institute of Human Morphology, 3 Tsurupa Street, 117418 Moscow, Russia.
J Pers Med. 2021 Sep 17;11(9):925. doi: 10.3390/jpm11090925.
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. : The aim of this study was to identify the estrogen-responsive genes that could be responsible for the exacerbation of psoriasis in menopausal women. : 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. : 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, and were not differentially expressed when we compared patients with and without menopause. All genes, except , were differentially expressed in patients with menopause compared to the volunteers with menopause. , , , and 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. : 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.
在女性中,银屑病的病程受女性生命周期各阶段的影响。根据先前的研究结果,性激素水平的显著变化会影响疾病的严重程度。本研究的目的是确定可能导致绝经后女性银屑病病情加重的雌激素反应基因。使用液相色谱 - 串联质谱法(LC-MS/MS)将银屑病患者(n = 5)捐赠的皮损皮肤样本与健康志愿者(n = 5)的皮肤样本进行比较。对差异表达蛋白质组进行蛋白质本体分析,以鉴定差异表达的雌激素反应蛋白。通过qPCR和ELISA对四组女性参与者验证所发现蛋白质的表达。第一组包括十名未绝经的银屑病患者;第二组包括十一名绝经后患者;第三组包括五名未绝经的健康志愿者;第四组包括六名绝经后志愿者。此外,参与者的血液样本用于评估雌二醇、孕酮和睾酮的水平。我们发现,与对照组相比,患者血液中雌二醇和孕酮水平显著降低,睾酮水平显著升高。LC-MS/MS数据的蛋白质本体分析确定了六种蛋白质,即血红素加氧酶1(HMOX1)、角蛋白19(KRT19)、乳酸脱氢酶A(LDHA)、热休克蛋白D1(HSPD1)、丝裂原活化蛋白激酶1(MAPK1)和碳酸酐酶2(CA2),与男性患者相比,在女性患者的皮损皮肤中差异表达。ELISA和qPCR实验证实了上述蛋白质及其mRNA的差异表达。与志愿者相比,编码上述蛋白质的基因在患者中差异表达。然而,当我们比较绝经和未绝经患者时,[此处原文缺失两个基因名称]没有差异表达。与绝经后志愿者相比,除[此处原文缺失一个基因名称]外,所有基因在绝经患者中均差异表达。与未绝经志愿者相比,[此处原文缺失四个基因名称]在未绝经患者中差异表达。然而,当我们比较绝经和未绝经的健康志愿者时,未发现显著变化。我们的实验发现女性患者皮肤中六个雌激素控制基因的差异表达。鉴定这些基因并评估其表达变化有助于深入了解雌激素在皮损皮肤中的生物学作用。蛋白质组学分析结果可通过ProteomeXchange获取,标识符为PXD021673。