The Model of <i>PPARγ</i>-Downregulated Signaling in Psoriasis

Соболев, В. В.; Nesterova, Anastasia P.; Соболева, А. Г.; Dvoriankova, Evgenia; Piruzyan, A. L.; Mildzikhova, D.R.; Korsunskaya, I. M.; Svitich, Oxana

doi:10.1155/2020/6529057

Cited by 11 publications

(9 citation statements)

References 51 publications

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“…Moreover, the activation of PPAR-γ also inhibits the differentiation of Th CD4 + cells to Th 17 cells. According to preliminary results, PPAR-γ controls ~150 genes directly associated with the disease [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

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

Соболев

Tchepourina

Korsunskaya

et al. 2022

IJMS

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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.

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Section: Introductionmentioning

confidence: 99%

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

Соболев

Tchepourina

Korsunskaya

et al. 2022

IJMS

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“…In published microarray data, the level of expression of RORC was downregulated in most of 58 patients [15,21].…”

Section: Figurementioning

confidence: 98%

“…In the last work we build the model that describes a hypothesis that low activity of PPARγ signaling may promote psoriasis. We applied network analysis to build the model and we used public microarrays data to find statistically significant molecular cascades, cell processes, molecular regulators and expression targets of PPARγ [15] (see Supplementary Materials).…”

Section: Introductionmentioning

confidence: 99%

Analysis of PPARγ Signaling Activity in Psoriasis

Соболев

Nesterova

Соболева

et al. 2021

IJMS

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In our previous work, we built the model of PPARγ dependent pathways involved in the development of the psoriatic lesions. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and transcription factor which regulates the expression of many proinflammatory genes. We tested the hypothesis that low levels of PPARγ expression promote the development of psoriatic lesions triggering the IL17-related signaling cascade. Skin samples of normally looking and lesional skin donated by psoriasis patients and psoriatic CD3+ Tcells samples (n = 23) and samples of healthy CD3+ T cells donated by volunteers (n = 10) were analyzed by real-time PCR, ELISA and immunohistochemistry analysis. We found that the expression of PPARγ is downregulated in human psoriatic skin and laser treatment restores the expression. The expression of IL17, STAT3, FOXP3, and RORC in psoriatic skin before and after laser treatment were correlated with PPARγ expression according to the reconstructed model of PPARγ pathway in psoriasis.In conclusion, we report that PPARγ weakens the expression of genes that contribute in the development of psoriatic lesion. Our data show that transcriptional regulation of PPARγ expression by FOSL1 and by STAT3/FOSL1 feedback loop may be central in the psoriatic skin and T-cells.

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“…PPARγ может действовать напрямую, отрицательно регулируя экспрессию провоспалительных генов лигандзависимым образом, противодействуя активности транскрипционных факторов. Продемонстрировано, что специфические лиганды PPARγ ингибируют продукцию многих медиаторов воспаления и цитокинов в различных типах клеток, включая моноциты, лимфоциты и эпителиальные клетки [45,46]. Зная, что псориаз представляет собой воспалительное заболевание кожи, характеризующееся гиперпролиферацией эпидермиса и аномальной дифференцировкой кератиноцитов, PPARγ может рассматриваться как новая потенциальная мишень для лечения [47].…”

Section: оригинальная статьяunclassified

Basic genetic and biological markers of psoriasis

et al. 2021

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Background. Psoriasis is a chronic inflammatory autoimmune disease characterized by an excessively aberrant hyperproliferation of keratinocytes. The pathogenesis of psoriasis is complex, and the exact mechanism, despite numerous studies, is still unclear. Complex genetic relationships play an important role in the pathogenesis of this skin disease. A large number of genes that are also associated with other diseases are involved in the development of psoriasis. The variety of comorbidities in patients with psoriasis often present challenges to the treatment for dermatosis. Understanding the role of certain genes in the pathogenesis of psoriasis will contribute the development of more effective targeted therapy aimed at blocking the corresponding inflammatory signaling pathways and molecules. Aim. To analyze and systematize the basic genetic and biological markers of psoriasis. Materials and methods. The study included research articles on the genetic analysis of psoriasis. The ResNet, PubMed and eLibrary databases were used. Results and discussion. Basic genetic and biological markers were identified by analysis of literature sources devoted to psoriasis. Attention is paid to the role and effects of single nucleotide polymorphisms, which make it possible to establish a clear association of a number of genes involved in the development of psoriasis. Genes with altered expression in the psoriatic process were considered separately. Conclusion. The identified biomarkers can be used in targeted biological therapy of psoriasis using biological modulators that block signaling.

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The Model of PPARγ-Downregulated Signaling in Psoriasis

Cited by 11 publications

References 51 publications

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

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

Analysis of PPARγ Signaling Activity in Psoriasis

Basic genetic and biological markers of psoriasis

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