Laser Therapy Changes the Expression of Matrix Metalloproteinases in Bleomycin-Induced Skin Fibrosis.

Matrix metalloproteinases (MMPs) are often considered biomarkers of skin fibrosis. At the early stages of the pathological process, an elevation of their enzymatic activity causes significant changes in the composition of the extracellular matrix. MMPs secreted by immune cells facilitate their migration to the site of damage. Then, the immune cells eliminate the affected cells and biomolecules. Moreover, bidirectional changes in the activity of proteolytic enzymes, including MMPs, accompany wound healing. This study aimed to assess changes in the expression of Mmp2, Mmp3, and Mmp9 after treating mice with laser therapy using the experimental model of bleomycin-induced skin fibrosis. Using immunohistochemistry, we characterized the histological features of scarred skin. We also analyzed changes in the expression of MMPs using real-time polymerase chain reaction before and after laser irradiation. We showed that treatment of the mice with a CO2 laser partially normalized the histological features of scarred skin. We also noticed a decrease in the expression of Mmp2, Mmp3 (both p < 0.05), and Mmp9 (p = 0.065) during scar healing. The obtained results suggest that normalization of skin homeostasis requires control of MMP activity via induction of genes.

The Role of Transcription Factor PPAR-γ in the Pathogenesis of Psoriasis, Skin Cells, and Immune Cells.

The peroxisome proliferator-activated receptor PPAR-γ is one of three PPAR nuclear receptors that act as ligand-activated transcription factors. In immune cells, the skin, and other organs, PPAR-γ regulates lipid, glucose, and amino acid metabolism. The receptor translates nutritional, pharmacological, and metabolic stimuli into the changes in gene expression. The activation of PPAR-γ promotes cell differentiation, reduces the proliferation rate, and modulates the immune response. In the skin, PPARs also contribute to the functioning of the skin barrier. Since we know that the route from identification to the registration of drugs is long and expensive, PPAR-γ agonists already approved for other diseases may also represent a high interest for psoriasis. In this review, we discuss the role of PPAR-γ in the activation, differentiation, and proliferation of skin and immune cells affected by psoriasis and in contributing to the pathogenesis of the disease. We also evaluate whether the agonists of PPAR-γ may become one of the therapeutic options to suppress the inflammatory response in lesional psoriatic skin and decrease the influence of comorbidities associated with psoriasis.

Proteomic Studies of Psoriasis.

In this review paper, we discuss the contribution of proteomic studies to the discovery of disease-specific biomarkers to monitor the disease and evaluate available treatment options for psoriasis. Psoriasis is one of the most prevalent skin disorders driven by a Th17-specific immune response. Although potential patients have a genetic predisposition to psoriasis, the etiology of the disease remains unknown. During the last two decades, proteomics became deeply integrated with psoriatic research. The data obtained in proteomic studies facilitated the discovery of novel mechanisms and the verification of many experimental hypotheses of the disease pathogenesis. The detailed data analysis revealed multiple differentially expressed proteins and significant changes in proteome associated with the disease and drug efficacy. In this respect, there is a need for proteomic studies to characterize the role of the disease-specific biomarkers in the pathogenesis of psoriasis, develop clinical applications to choose the most efficient treatment options and monitor the therapeutic response.

Role of the Transcription Factor FOSL1 in Organ Development and Tumorigenesis.

The transcription factor FOSL1 plays an important role in cell differentiation and tumorigenesis. Primarily, FOSL1 is crucial for the differentiation of several cell lineages, namely adipocytes, chondrocytes, and osteoblasts. In solid tumors, FOSL1 controls the progression of tumor cells through the epithelial-mesenchymal transformation. In this review, we summarize the available data on FOSL1 expression, stabilization, and degradation in the cell. We discuss how FOSL1 is integrated into the intracellular signaling mechanisms and provide a comprehensive analysis of FOSL1 influence on gene expression. We also analyze the pathological changes caused by altered Fosl1 expression in genetically modified mice. In addition, we dedicated a separate section of the review to the role of FOSL1 in human cancer. Primarily, we focus on the FOSL1 expression pattern in solid tumors, FOSL1 importance as a prognostic factor, and FOSL1 perspectives as a molecular target for anticancer therapy.

PDE4B gene polymorphism in Russian patients with panic disorder.

BACKGROUND: Panic disorder is a complex disease of unclear etiology but with an apparent genetic component. PDE4B gene product is involved in many cell processes owing to its function-regulation of the level of a second messenger cAMP. PDE4B gene polymorphism has been shown to be associated with some mental disorders including panic disorder. AIMS: The goal of our study was to evaluate the role of 3 SNPs in the PDE4B gene in the development of panic disorder. METHODS: 94 patients diagnosed with panic disorder according to the DSM-IV criteria were enrolled in the study. The population control group included 192 subjects. Genotyping was carried out by real-time PCR with TaqMan probes. RESULTS: The investigated substitutions are not associated with panic disorder in general and in female/male cohorts (p > 0.05). The analysis of complex genotypes demonstrated two protective complex genotypes (rs1040716:A, T + rs10454453:A + rs502958:A and rs1040716:A, T + rs502958:A) associated with panic disorder in general regardless of the patient's gender (p < 0.05). These genotypes did not correlate with the patient's sex. CONCLUSIONS: We found two complex protective genotypes associated with panic disorder. This can be due to the fact that predisposition to the disease are associated with other genes, while PDE4B gene polymorphism reduces their effect.