Sergey Bruskin

Integrated network analysis of transcriptomic and proteomic data in psoriasis

BackgroundPsoriasis is complex inflammatory skin pathology of autoimmune origin. Several cell types are perturbed in this pathology, and underlying signaling events are complex and still poorly understood.ResultsIn order to gain insight into molecular machinery underlying the disease, we conducted a comprehensive meta-analysis of proteomics and transcriptomics of psoriatic lesions from independent studies. Network-based analysis revealed similarities in regulation at both proteomics and transcriptomics level. We identified a group of transcription factors responsible for overexpression of psoriasis genes and a number of previously unknown signaling pathways that may play a role in this process. We also evaluated functional synergy between transcriptomics and proteomics results.ConclusionsWe developed network-based methodology for integrative analysis of high throughput data sets of different types. Investigation of proteomics and transcriptomics data sets on psoriasis revealed versatility in regulatory machinery underlying pathology and showed complementarities between two levels of cellular organization.

Characterization of three Arabidopsis thaliana immunophilin genes involved in the plant defense response against Pseudomonas syringae.

Plant immunophilins are a broadly conserved family of proteins, which carry out a variety of cellular functions. In this study, we investigated three immunophilin genes involved in the Arabidopsis thaliana response to Pseudomonas syringae infection: a cytoplasmic localized AtCYP19, a cytoplasmic and nuclear localized AtCYP57, and one nucleus directed FKBP known as AtFKBP65. Arabidopsis knock-out mutations in these immunophilins result in an increased susceptibility to P. syringae, whereas overexpression of these genes alters the transcription profile of pathogen-related defense genes and led to enhanced resistance. Histochemical analysis revealed local gene expression of AtCYP19, AtCYP57, and AtFKBP65 in response to pathogen infection. AtCYP19 was shown to be involved in reactive oxygen species production, and both AtCYP57 and AtFKBP65 provided callose accumulation in plant cell wall. Identification of the involvement of these genes in biotic stress response brings a new set of data that will advance plant immune system research and can be widely used for further investigation in this area.

Matrix metalloproteinases and their role in psoriasis.

This review summarizes the contribution of matrix metalloproteinases to the pathogenesis of psoriasis. In psoriasis, matrix metalloproteinases are involved in the structural changes of the epidermis via the modification of intracellular contacts and the composition of the extracellular matrix, promoting angiogenesis in the dermal blood vessels and the infiltration of immune cells. Moreover, some matrix metalloproteinases become differentially expressed during the disease eruption and their expression correlates with the clinical score. A separate section of the review is dedicated to the pharmacological approaches that are used to control matrix metalloproteinases, such as oral metalloproteinase inhibitors, such as azasugars and phosphonamides. The aim of this manuscript is to assess the role of matrix metalloproteinases in the physiological processes that accompany the disease. Moreover, it is especially important to evaluate progress in this field and characterize recently appeared medicines. Because any experimental drugs that target matrix metalloproteinases are involved in active clinical trials, this manuscript also reviews the latest experimental data regarding distribution and expression of matrix metalloproteinases in healthy skin and lesional skin. Therefore, the performed analysis highlights potential problems associated with the use of metalloproteinase inhibitors in clinical studies and suggests simple and easy understandable criteria that future innovative metalloproteinase inhibitors shall satisfy.

Genes expression of metalloproteinases (MMP-1, MMP-2, MMP-9, and MMP-12) associated with psoriasis

Using real-time polymerase chain reaction (RT-PCR), we measured mRNA amounts of matrix metalloproteinases (MMPs): MMP-1, MMP-2, MMP-9, and MMP-12 genes in psoriatic lesions and unaffected skin of the same patients. We observed significant (about 15-fold) increase in the expression level of matrix metalloproteinase MMP-1 and MMP-12 genes associated with psoriasis. The results of our studies of MMP gene expression in cultured primary human keratinocytes treated with interleukin (IL)-17 have shown upregulation of MMP gene expression both in cultured keratinocytes and in psoriatic skin lesions. Therefore, upregulation of MMP genes in the skin affected by psoriasis could result from IL-17 effects on skin cells.

Laccase multigene families in Agaricomycetes

Here we present the results of the exploration of laccase multigene families (MGFs) in basidiomycetous fungi from different taxonomic groups using a next generation sequencing (NGS) technology. In our study, multiple laccase genes were identified in all of the investigated fungi (13 species) from Polyporaceae, Phanerochaetaceae, Meruliaceae, Pleurotaceae, Physalacriaceae, and Peniophoraceae families. It was shown that phylogenetic positioning of the newly identified sequences exhibit patterns of clusterization with respect to enzyme properties. This can be a potentially useful tool for selecting naturally existing laccases with different physicochemical characteristics relevant to different biotechnological applications. Moreover, the method developed in this study can be used in the screening of environmental samples and fast characterization of laccase MGFs in newly identified fungal species.

Diacylglyceryltrimethylhomoserine content and gene expression changes triggered by phosphate deprivation in the mycelium of the basidiomycete Flammulina velutipes

Diacylglyceryltrimethylhomoserines (DGTS) are betaine-type lipids that are phosphate-free analogs of phosphatidylcholines (PC). DGTS are abundant in some bacteria, algae, primitive vascular plants and fungi. In this study, we report inorganic phosphate (Pi) deficiency-induced DGTS synthesis in the basidial fungus Flammulina velutipes (Curt.: Fr.) Sing. We present results of an expression analysis of the BTA1 gene that codes for betaine lipid synthase and two genes of PC biosynthesis (CHO2 and CPT1) during phosphate starvation of F. velutipes culture. We demonstrate that FvBTA1 gene has increased transcript abundance under phosphate starvation. Despite depletion in PC, both CHO2 and CPT1 were determined to have increased expression. We also describe the deduced amino acid sequence and genomic structure of the BTA1 gene in F. velutipes. Phylogenetic relationships between putative orthologs of BTA1 proteins of basidiomycete fungi are discussed.

Three-Dimensional Skin Models of Psoriasis

Three-dimensional models of psoriatic skin occupy an intermediate position between cell cultures and animal-based models. Unlike cultured cells, they closely imitate changes in cell differentiation and metabolism, which are characteristic of psoriatic lesional skin. Because 3-dimensional models exclude nonspecific influences of the surrounding organs and tissues, in some studies they are preferred over animal-based models. Moreover, 3-dimensional models can be used for drug screening and testing new pharmacological approaches. In this paper, we discuss how 3-dimensional models of psoriatic lesional skin were created and developed. We also analyze their prospects in experimental studies of psoriasis.

The role of peptidyl-prolyl cis/trans isomerase genes of Arabidopsis thaliana in plant defense during the course of Xanthomonas campestris infection

Experimental data obtained in this study had shown the involvement of A. thaliana immunophilin genes At2g16600, At4g33060, and At5g48570 in plant defense responses to the Xanthomonas campestris invasion. We had found not only that the expression levels of these genes changed upon bacterial infection, but also that the plant’s resistance to the pathogen was increased if the expression levels of the immunophilin genes were elevated in the host cells.

Genetically modified animals as models of the pathological processes in psoriasis

Psoriasis is a chronic recurrent disorder that affects predominantly the skin and is autoimmune in nature. Experimental models help to study the development of psoriasis in controlled conditions and investigate particular aspects of the pathological process. Many mouse models were obtained to reproduce, to a certain extent, the psoriasis signs seen in humans. Genetically modified animals help to reveal the new genes whose mutations potentially underlie the disease and to search for new therapeutic targets. Moreover, the animal models are used to test new drugs and therapies. The review summarizes the published data on the laboratory animal models of the psoriatic process.

Role of receptor for advanced glycation end-products in pathogenesis of psoriasis

This review summarizes the existing knowledge regarding the role of receptor for advanced glycation end products in pathogenesis of psoriasis. This receptor plays a crucial role in the inflammatory response. By interacting with multiple ligands and activating several signaling mechanisms, receptor for advanced glycation end products regulates gene expression via a group of well-characterized transcription factors, such as NFkB and AP1. The expression of receptor for advanced glycation end products in both immune cells and their targets, a high stability of this receptor in complexes with ligands as well as a positive feedback loop, upregulating the expression of its certain ligands, suggest receptor for advanced glycation end products as a possible principal factor that promotes the development of psoriasis. Considering receptor for advanced glycation end products as a potential master regulator of several processes that play a crucial role in development of psoriatic plaques, we believe that further experimental studies are needed to elucidate how exactly this receptor converts a transient inflammatory reaction to a sustainable inflammatory response. These studies are also needed for the development of novel medications that target receptor for advanced glycation end products and signaling mechanisms that this receptor activates.