Genetically modified animals as models of the pathological processes in psoriasis

Соболева, А. Г.; Mesentsev, Alexandre; Брускин, С. А.

doi:10.1134/s0026893314040153

Cited by 4 publications

(3 citation statements)

References 93 publications

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“…Primarily, it significantly increases the proliferation of epidermal keratinocytes (rev. in [ 128 ]). Moreover, grafting the skin cells expressing a dominant-negative mutant IκBα on immunocompromised mice produces psoriasis-like skin lesions [ 129 ].…”

Section: The Role Of Ppar-γ In Skin Metabolismmentioning

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: The Role Of Ppar-γ In Skin Metabolismmentioning

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 psoriatic skin, lymphocytes may alter the epidermal growth resulting in keratinocyte hyperproliferation and abnormal differentiation of apoptotic cells. 104 Various experimental animal models have been developed for psoriasis, namely, asebia mouse, 105 flaky skin mouse, 106 ultraviolet ray-B induced photodermatitis model, 107 genetically modified models of psoriasiform skin diseases, 108 and mouse tail model. [56][57][58][59][60] In this study, mouse tail model was selected to to avoidance of direct contact of its acidic functional group (−COOH), the trigger factor for irritation episodes, with the SC of the skin.…”

Section: Histopathologic Examinationmentioning

confidence: 99%

Pivotal role of Acitretin nanovesicular gel for effective treatment of psoriasis: ex vivo–in vivo evaluation study

Hashim

El-Magd

El‐Sheakh

et al. 2018

IJN

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The goal of the current study was to explore the potential benefits of Acitretin (Act) nanovesicular gel as a prospective antipsoriatic topical delivery system counteracting the drug challenges in terms of its extremely low aqueous solubility, instability, skin irritation, and serious systemic adverse effects. Act-loaded niosomes were successfully developed, entirely characterized, and optimized. Further evaluation of the optimized formula was conducted regarding its stability and ex vivo cytotoxicity on different cell lines. The optimized niosomal vesicles were then incorporated in gel base matrix and investigated by sequential ex vivo (skin permeation and deposition) and in vivo (skin irritation and antipsoriatic activity using mouse tail model) experiments. The optimized Act-loaded niosomes (span 60:cholesterol molar ratio 1:1) were spherical in shape and exhibited the highest entrapment efficiency (90.32±3.80%) with appropriate nanosize and zeta potential of 369.73±45.45 nm and −36.33±1.80 mV, respectively. Encapsulation of the drug in the nanovesicles was further emphasized by differential scanning calorimetric and powder X-ray diffraction studies. After 3 months storage at 4±1°C, the optimized formula preserved its stability. Act nano niosomal gel produced a remarkable enhanced ex vivo permeation profile up to 30 h and significant drug deposition in the viable epidermal–dermal layers compared with those of Act gel. The pronounced antipsoriatic activity of the medicated nano niosomes was proved ex vivo in HaCaT cells (a keratinocyte cell line). Topical application of Act nano niosomal gel to mouse tail model further established its distinct in vivo antipsoriatic superiority in terms of significantly higher orthokeratosis, drug activity, and reduction in epidermal thickness compared with the control and other gel formulations. Also, negligible skin irritation and better skin tolerability of Act nanovesicular gel were revealed by primary irritation index and histopathologic examination.

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“…Murine models showing psoriasiform inflammation have been extensively used and they vary from genetic (spontaneous mutation, transgenic or knockout models) and "ligand" induced models, like the widely used imiquimod model. Multiple reviews have summarized the animals models used to study psoriasis research, [31][32][33][34][35] and to date, many of these models are still used for preclinical studies on newly developed therapies.…”

Section: Model S To S Tudy Psoria S Ismentioning

confidence: 99%

Past, present and future of in vitro 3D reconstructed inflammatory skin models to study psoriasis

Niehues

Bogaard

2018

Experimental Dermatology

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Psoriasis is a common chronic inflammatory disease affecting about 1%-2% of today's Western population.[1] Several subtypes of psoriasis are known, but herein we focus on psoriasis vulgaris which is most prevalent and phenotypically characterized by sharply demarcated plaques covered with white scales. The pathogenesis of psoriasis is complex and exact mechanisms of disease onset and manifestation remain unknown. However, it is known that psoriasis cannot be attributed to a single risk factor or insult but is likely caused by the interaction of environmental and genetic factors. Based on a number of genomewide association studies (GWAS) and meta-analyses thereof, more than 60 susceptibility loci have been identified that account for 20%-25% of psoriasis heritability. [2][3][4][5][6][7] Although psoriasis has been regarded as an (auto) immune disease for a long time, an increasing body of evidence directs towards a combined role for the innate and adaptive immune system in combination with tissue specific epidermal factors. AbstractPsoriasis is a common chronic inflammatory skin disease with a significant socioeconomic impact that can greatly affect the patients' quality of life. The prevailing dogma in the aetiology and pathophysiology of this complex disease is that skin cells, immune cells and environmental factors contribute to psoriatic skin inflammation.For a better understanding of the disease pathogenesis, models are required that mimic the disease and which can be used to develop therapeutics. Over the last decades, in vitro human reconstructed skin models have been widely used in dermatological research and have also been developed to mimic psoriatic skin. This viewpoint summarizes the most commonly used in vitro models and the latest accomplishments for the combination of the dermal and epidermal compartments with other cell types

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Genetically modified animals as models of the pathological processes in psoriasis

Cited by 4 publications

References 93 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

Pivotal role of Acitretin nanovesicular gel for effective treatment of psoriasis: ex vivo–in vivo evaluation study

Past, present and future of in vitro 3D reconstructed inflammatory skin models to study psoriasis

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Genetically modified animals as models of the pathological processes in psoriasis

Cited by 4 publications

References 93 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

Pivotal role of Acitretin nanovesicular gel for effective treatment of psoriasis: ex vivo&ndash;in vivo evaluation study

Past, present and future of in vitro 3D reconstructed inflammatory skin models to study psoriasis

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Product

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Pivotal role of Acitretin nanovesicular gel for effective treatment of psoriasis: ex vivo–in vivo evaluation study