scholarly journals Differential Expression of Estrogen-Responsive Genes in Women with Psoriasis

2021 ◽  
Vol 11 (9) ◽  
pp. 925
Author(s):  
Vladimir Sobolev ◽  
Anna Soboleva ◽  
Elena Denisova ◽  
Malika Denieva ◽  
Eugenia Dvoryankova ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Differential Expression ◽  
Biological Effects ◽  
Differentially Expressed ◽  
Lesional Skin ◽  
Female Patients ◽  
Genes Encoding ◽  
Liquid Chromatography Tandem Mass ◽  
Severity Of The Disease ◽  
Skin Samples

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.

scholarly journals LC-MS/MS analysis of lesional and normally looking psoriatic skin reveals significant changes in protein metabolism and RNA processing

2020 ◽  
Author(s):  
V.V. Sobolev ◽  
R.H. Ziganshin ◽  
A.V. Mezentsev ◽  
A.G. Soboleva ◽  
M. Denieva ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Rna Processing ◽  
Protein Identification ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Psoriatic Skin ◽  
Differentially Expressed Proteins ◽  
Kinin System ◽  
Lesional Skin ◽  
Kallikrein Kinin System

AbstractBackgroundPlaque psoriasis is a chronic autoimmune disorder characterized by the development of red scaly plaques. To date psoriasis lesional skin transcriptome has been extensively studied, whereas only few proteomic studies of psoriatic skin are available.AimThe aim of this study was to compare protein expression patterns of lesional and normally looking skin of psoriasis patients with skin of the healthy volunteers, reveal differentially expressed proteins and identify changes in cell metabolism caused by the disease.MethodsSkin samples of normally looking and lesional skin donated by psoriasis patients (n = 5) and samples of healthy skin donated by volunteers (n = 5) were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After protein identification and data processing, the set of differentially expressed proteins was subjected to protein ontology analysis to characterize changes in biological processes, cell components and molecular functions in the patients’ skin compared to skin of the healthy volunteers.ResultsThe performed analysis identified 405 and 59 differentially expressed proteins in lesional and normally looking psoriatic skin compared to healthy control. We discovered decreased expression of KNG1, APOE, HRG, THBS1 and PLG in normally looking skin of the patients. Presumably, these changes were needed to protect the epidermis from spontaneous activation of kallikrein-kinin system and delay the following development of inflammatory response. In lesional skin, we identified several large groups of proteins with coordinated expression. Mainly, these proteins were involved in different aspects of protein and RNA metabolism, namely ATP synthesis and consumption; intracellular trafficking of membrane-bound vesicles, pre-RNA processing, translation, chaperoning and degradation in proteasomes/immunoproteasomes.ConclusionOur findings explain the molecular basis of metabolic changes caused by disease in skin lesions, such as faster cell turnover and higher metabolic rate. They also indicate on downregulation of kallikrein-kinin system in normally looking skin of the patients that would be needed to delay exacerbation of the disease. Data are available via ProteomeXchange with identifier PXD021673.

scholarly journals LC-MS/MS analysis of lesional and normally looking psoriatic skin reveals significant changes in protein metabolism and RNA processing

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0240956
Author(s):  
V. V. Sobolev ◽  
A. V. Mezentsev ◽  
R. H. Ziganshin ◽  
A. G. Soboleva ◽  
M. Denieva ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Rna Processing ◽  
Protein Identification ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Psoriatic Skin ◽  
Differentially Expressed Proteins ◽  
Kinin System ◽  
Lesional Skin ◽  
Kallikrein Kinin System

Background Plaque psoriasis is a chronic autoimmune disorder characterized by the development of red scaly plaques. To date psoriasis lesional skin transcriptome has been extensively studied, whereas only few proteomic studies of psoriatic skin are available. Aim The aim of this study was to compare protein expression patterns of lesional and normally looking skin of psoriasis patients with skin of the healthy volunteers, reveal differentially expressed proteins and identify changes in cell metabolism caused by the disease. Methods Skin samples of normally looking and lesional skin donated by psoriasis patients (n = 5) and samples of healthy skin donated by volunteers (n = 5) were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After protein identification and data processing, the set of differentially expressed proteins was subjected to protein ontology analysis to characterize changes in biological processes, cell components and molecular functions in the patients’ skin compared to skin of the healthy volunteers. The expression of selected differentially expressed proteins was validated by ELISA and immunohistochemistry. Results The performed analysis identified 405 and 59 differentially expressed proteins in lesional and normally looking psoriatic skin compared to healthy control. In normally looking skin of the patients, we discovered decreased expression of KNG1, APOE, HRG, THBS1 and PLG. Presumably, these changes were needed to protect the epidermis from spontaneous activation of kallikrein-kinin system and delay the following development of inflammatory response. In lesional skin, we identified several large groups of proteins with coordinated expression. Mainly, these proteins were involved in different aspects of protein and RNA metabolism, namely ATP synthesis and consumption; intracellular trafficking of membrane-bound vesicles, pre-RNA processing, translation, chaperoning and degradation in proteasomes/immunoproteasomes. Conclusion Our findings explain the molecular basis of metabolic changes caused by disease in skin lesions, such as faster cell turnover and higher metabolic rate. They also indicate on downregulation of kallikrein-kinin system in normally looking skin of the patients that would be needed to delay exacerbation of the disease. Data are available via ProteomeXchange with identifier PXD021673.

scholarly journals Optimization of the molecular genetics for the diagnosis of early mycosis fungoides

2021 ◽  
Vol 24 (1) ◽  
pp. 35-44
Author(s):  
Olga Yu. Olisova ◽  
Ekaterina V. Grekova ◽  
Ekaterina A. Alekseeva ◽  
Dmitry V. Zaletaev
Keyword(s):  
Gene Expression ◽  
Early Diagnosis ◽  
Healthy Volunteers ◽  
Mycosis Fungoides ◽  
Diagnostic Algorithm ◽  
Control Group ◽  
Common Disease ◽  
Lesional Skin ◽  
T Cell Lymphomas ◽  
Skin Samples

BACKGROUND: Mycosis fungoides (MF) is the most common disease among the cutaneous T-cell lymphomas (8590%). The accuracy of the diagnosis of MF, which is confirmed only by clinical, histological and immunohistochemical signs, is 5075%. AIMS: To investigate genetic marker STAT4 for early diagnosis of mycosis fungoides. MATERIALS AND METHODS: A study involving 42 patients with MF and chronic benign dermatoses (CBD) was performed. The analysis of gene expression STAT4 was carried out by TaqMan Real time-PCR. The objects of the study were lesional skin samples of patients. A group with MF consisted of 29 patients, a group with CBD consisted of 13 patients, a control group included 10 healthy volunteers. RESULTS: The study revealed that the level of STAT4 gene expression showed a significant (9 times) increase in the expression of gene STAT4 in patients with MF (168.2) compared with patients with CBD (18.5; p 0.001) and 561 times with healthy volunteers (0.3; p 0.001). CONCLUSION: For early diagnosis of MF the level of expression STAT4 is of great importance. Inclusion of STAT4 in the list of diagnostic algorithm increases the accuracy of differential diagnosis of MF and CBD from 59.1 to 92.2%.

Decoding Psoriasis: Integrated Bioinformatics Approach to Understand Hub Genes and Involved Pathways

2020 ◽  
Vol 26 (29) ◽  
pp. 3619-3630
Author(s):  
Saumya Choudhary ◽  
Dibyabhaba Pradhan ◽  
Noor S. Khan ◽  
Harpreet Singh ◽  
George Thomas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Gene ◽  
Therapeutic Targets ◽  
Interaction Network ◽  
Gene Expression Omnibus ◽  
Differentially Expressed ◽  
Keratinocyte Differentiation ◽  
Hub Genes ◽  
Lesional Skin ◽  
Ncbi Gene Expression Omnibus

Background: Psoriasis is a chronic immune mediated skin disorder with global prevalence of 0.2- 11.4%. Despite rare mortality, the severity of the disease could be understood by the accompanying comorbidities, that has even led to psychological problems among several patients. The cause and the disease mechanism still remain elusive. Objective: To identify potential therapeutic targets and affecting pathways for better insight of the disease pathogenesis. Method: The gene expression profile GSE13355 and GSE14905 were retrieved from NCBI, Gene Expression Omnibus database. The GEO profiles were integrated and the DEGs of lesional and non-lesional psoriasis skin were identified using the affy package in R software. The Kyoto Encyclopaedia of Genes and Genomes pathways of the DEGs were analyzed using clusterProfiler. Cytoscape, V3.7.1 was utilized to construct protein interaction network and analyze the interactome map of candidate proteins encoded in DEGs. Functionally relevant clusters were detected through Cytohubba and MCODE. Results: A total of 1013 genes were differentially expressed in lesional skin of which 557 were upregulated and 456 were downregulated. Seven dysregulated genes were extracted in non-lesional skin. The disease gene network of these DEGs revealed 75 newly identified differentially expressed gene that might have a role in development and progression of the disease. GO analysis revealed keratinocyte differentiation and positive regulation of cytokine production to be the most enriched biological process and molecular function. Cytokines -cytokine receptor was the most enriched pathways. Among 1013 identified DEGs in lesional group, 36 DEGs were found to have altered genetic signature including IL1B and STAT3 which are also reported as hub genes. CCNB1, CCNA2, CDK1, IL1B, CXCL8, MKI 67, ESR1, UBE2C, STAT1 and STAT3 were top 10 hub gene. Conclusion: The hub genes, genomic altered DEGs and other newly identified differentially dysregulated genes would improve our understanding of psoriasis pathogenesis, moreover, the hub genes could be explored as potential therapeutic targets for psoriasis.

scholarly journals Differential Gene Expression between Fungal Mating Types Is Associated with Sequence Degeneration

2020 ◽  
Vol 12 (4) ◽  
pp. 243-258 ◽  
Author(s):  
Wen-Juan Ma ◽  
Fantin Carpentier ◽  
Tatiana Giraud ◽  
Michael E Hood
Keyword(s):  
Differential Expression ◽  
Differentially Expressed Genes ◽  
Mating Type ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Gc Content ◽  
Differentially Expressed ◽  
Mating Types ◽  
Sexual Antagonism ◽  
Recombination Suppression

Abstract Degenerative mutations in non-recombining regions, such as in sex chromosomes, may lead to differential expression between alleles if mutations occur stochastically in one or the other allele. Reduced allelic expression due to degeneration has indeed been suggested to occur in various sex-chromosome systems. However, whether an association occurs between specific signatures of degeneration and differential expression between alleles has not been extensively tested, and sexual antagonism can also cause differential expression on sex chromosomes. The anther-smut fungus Microbotryum lychnidis-dioicae is ideal for testing associations between specific degenerative signatures and differential expression because 1) there are multiple evolutionary strata on the mating-type chromosomes, reflecting successive recombination suppression linked to mating-type loci; 2) separate haploid cultures of opposite mating types help identify differential expression between alleles; and 3) there is no sexual antagonism as a confounding factor accounting for differential expression. We found that differentially expressed genes were enriched in the four oldest evolutionary strata compared with other genomic compartments, and that, within compartments, several signatures of sequence degeneration were greater for differentially expressed than non-differentially expressed genes. Two particular degenerative signatures were significantly associated with lower expression levels within differentially expressed allele pairs: upstream insertion of transposable elements and mutations truncating the protein length. Other degenerative mutations associated with differential expression included nonsynonymous substitutions and altered intron or GC content. The association between differential expression and allele degeneration is relevant for a broad range of taxa where mating compatibility or sex is determined by genes located in large regions where recombination is suppressed.

scholarly journals Differential Expression of Serum Exosome microRNAs and Cytokines in Influenza A and B Patients Collected in the 2016 and 2017 Influenza Seasons

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 149
Author(s):  
Sreekumar Othumpangat ◽  
William G. Lindsley ◽  
Donald H. Beezhold ◽  
Michael L. Kashon ◽  
Carmen N. Burrell ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Influenza A ◽  
Influenza Infection ◽  
Cell Types ◽  
Airway Epithelial Cells ◽  
Differentially Expressed ◽  
Influenza B ◽  
Airway Epithelial ◽  
Monocyte Chemoattractant Protein 1 ◽  
Novel Approach

MicroRNAs (miRNAs) have remarkable stability and are key regulators of mRNA transcripts for several essential proteins required for the survival of cells and replication of the virus. Exosomes are thought to play an essential role in intercellular communications by transporting proteins and miRNAs, making them ideal in the search for biomarkers. Evidence suggests that miRNAs are involved in the regulation of influenza virus replication in many cell types. During the 2016 and 2017 influenza season, we collected blood samples from 54 patients infected with influenza and from 30 healthy volunteers to identify the potential role of circulating serum miRNAs and cytokines in influenza infection. Data comparing the exosomal miRNAs in patients with influenza B to healthy volunteers showed 76 miRNAs that were differentially expressed (p < 0.05). In contrast, 26 miRNAs were differentially expressed between patients with influenza A (p < 0.05) and the controls. Of these miRNAs, 11 were commonly expressed in both the influenza A and B patients. Interferon (IFN)-inducing protein 10 (IP-10), which is involved in IFN synthesis during influenza infection, showed the highest level of expression in both influenza A and B patients. Influenza A patients showed increased expression of IFNα, GM-CSF, interleukin (IL)-13, IL-17A, IL-1β, IL-6 and TNFα, while influenza B induced increased levels of EGF, G-CSF, IL-1α, MIP-1α, and TNF-β. In addition, hsa-miR-326, hsa-miR-15b-5p, hsa-miR-885, hsa-miR-122-5p, hsa-miR-133a-3p, and hsa-miR-150-5p showed high correlations to IL-6, IL-15, IL-17A, IL-1β, and monocyte chemoattractant protein-1 (MCP-1) with both strains of influenza. Next-generation sequencing studies of H1N1-infected human lung small airway epithelial cells also showed similar pattern of expression of miR-375-5p, miR-143-3p, 199a-3p, and miR-199a-5p compared to influenza A patients. In summary, this study provides insights into the miRNA profiling in both influenza A and B virus in circulation and a novel approach to identify the early infections through a combination of cytokines and miRNA expression.

scholarly journals High heterogeneity undermines generalization of differential expression results in RNA-Seq analysis

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Weitong Cui ◽  
Huaru Xue ◽  
Lei Wei ◽  
Jinghua Jin ◽  
Xuewen Tian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Expression ◽  
Small Sample ◽  
Differentially Expressed ◽  
Cancer Type ◽  
Rna Seq ◽  
Sample Sizes ◽  
Large Sample ◽  
Expression Levels ◽  
Gene Expression Levels

Abstract Background RNA sequencing (RNA-Seq) has been widely applied in oncology for monitoring transcriptome changes. However, the emerging problem that high variation of gene expression levels caused by tumor heterogeneity may affect the reproducibility of differential expression (DE) results has rarely been studied. Here, we investigated the reproducibility of DE results for any given number of biological replicates between 3 and 24 and explored why a great many differentially expressed genes (DEGs) were not reproducible. Results Our findings demonstrate that poor reproducibility of DE results exists not only for small sample sizes, but also for relatively large sample sizes. Quite a few of the DEGs detected are specific to the samples in use, rather than genuinely differentially expressed under different conditions. Poor reproducibility of DE results is mainly caused by high variation of gene expression levels for the same gene in different samples. Even though biological variation may account for much of the high variation of gene expression levels, the effect of outlier count data also needs to be treated seriously, as outlier data severely interfere with DE analysis. Conclusions High heterogeneity exists not only in tumor tissue samples of each cancer type studied, but also in normal samples. High heterogeneity leads to poor reproducibility of DEGs, undermining generalization of differential expression results. Therefore, it is necessary to use large sample sizes (at least 10 if possible) in RNA-Seq experimental designs to reduce the impact of biological variability and DE results should be interpreted cautiously unless soundly validated.

scholarly journals A Practical Multifaceted Approach to Selecting Differentially Expressed Genes

2007 ◽  
Vol 3 ◽  
pp. 117693510700300
Author(s):  
Yingye Zheng ◽  
Margaret Pepe
Keyword(s):  
Differential Expression ◽  
Gene Selection ◽  
Error Rates ◽  
Cancer Prognosis ◽  
Differentially Expressed ◽  
Expression Array ◽  
Statistical Research ◽  
P Values ◽  
Control Error ◽  
Strength Of Evidence

Consider a gene expression array study comparing two groups of subjects where the goal is to explore a large number of genes in order to select for further investigation a subset that appear to be differently expressed. There has been much statistical research into the development of formal methods for designating genes as differentially expressed. These procedures control error rates such as the false detection rate or family wise error rate. We contend however that other statistical considerations are also relevant to the task of gene selection. These include the extent of differential expression and the strength of evidence for differential expression at a gene. Using real and simulated data we first demonstrate that a proper exploratory analysis should evaluate these aspects as well as decision rules that control error rates. We propose a new measure called the mp-value that quantifies strength of evidence for differential expression. The mp-values are calculated with a resampling based algorithm taking into account the multiplicity and dependence encountered in microarray data. In contrast to traditional p-values our mp-values do not depend on specification of a decision rule for their definition. They are simply descriptive in nature. We contrast the mp-values with multiple testing p-values in the context of data from a breast cancer prognosis study and from a simulation model.

scholarly journals Transcriptomic responses of Microcystis aeruginosa under electromagnetic radiation exposure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chao Tang ◽  
Ziyan Zhang ◽  
Shen Tian ◽  
Peng Cai
Keyword(s):  
Energy Metabolism ◽  
Electromagnetic Radiation ◽  
Differentially Expressed Genes ◽  
Microcystis Aeruginosa ◽  
Carbon Fixation ◽  
Biological Effects ◽  
Differentially Expressed ◽  
Ecological Environment ◽  
Inhibit Protein Synthesis ◽  
Potential Threat

AbstractElectromagnetic radiation is an important environmental factor. It has a potential threat to public health and ecological environment. However, the mechanism by which electromagnetic radiation exerts these biological effects remains unclear. In this study, the effect of Microcystis aeruginosa under electromagnetic radiation (1.8 GHz, 40 V/m) was studied by using transcriptomics. A total of 306 differentially expressed genes, including 121 upregulated and 185 downregulated genes, were obtained in this study. The differentially expressed genes were significantly enriched in the ribosome, oxidative phosphorylation and carbon fixation pathways, indicating that electromagnetic radiation may inhibit protein synthesis and affect cyanobacterial energy metabolism and photosynthesis. The total ATP synthase activity and ATP content significantly increased, whereas H+K+-ATPase activity showed no significant changes. Our results suggest that the energy metabolism pathway may respond positively to electromagnetic radiation. In the future, systematic studies on the effects of electromagnetic radiation based on different intensities, frequencies, and exposure times are warranted; to deeply understand and reveal the target and mechanism of action of electromagnetic exposure on organisms.

Sign in / Sign up

Export Citation Format

Share Document