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Psoriatic Arthritis and Skin Diseases: Pathogenesis and Therapies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 11888

Special Issue Editors


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Guest Editor
Department of Dermatology, Pediatric Dermatology and Dermatological Oncology, Medical University of Lodz, 91-347 Lodz, Poland
Interests: autoinflammatory and autoimmune skin diseases; photobiology and phototherapy
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Dermatology, Pediatric Dermatology and Dermatological Oncology, Medical University of Lodz, 92-215 Lodz, Poland
Interests: atopic dermatitis; photosensitivity; allergy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Almost every day we discover new data on our understanding and treatment of many diseases. The progress observed in psoriatic arthritis and skin disease pathogenesis and treatment over recent years has been outstanding; however, there are still many gaps in our knowledge. I would like to invite you to participate in the most recent achievements in the field of psoriatic arthritis and skin disorders. We welcome submissions of original and review papers on molecular mechanisms involved in pathogenesis and treatment of those diseases to the Special Issue titled: “Psoriatic Arthritis and Skin Diseases: Pathogenesis and Therapies”. Clinical studies with biomolecular experiments as well as case reports/series with a molecular element are also invited. Our aim is to present current views and results of experiments to provide the readers with an overview of the state of the art in this topic.

Prof. Dr. Joanna Narbutt
Dr. Malgorzata Skibinska
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • psoriatic arthritis
  • autoinflammatory skin diseases
  • psoriasis
  • atopic dermatitis
  • biological medications
  • inflammation
  • therapy
  • genetics

Published Papers (6 papers)

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Research

21 pages, 4716 KiB  
Article
Antiproliferative and Anti-Inflammatory Effects of the Polyphenols Phloretin and Balsacone C in a Coculture of T Cells and Psoriatic Keratinocytes
by Yasmine Ruel, Fatma Moawad, Jérôme Alsarraf, André Pichette, Jean Legault, Davide Brambilla and Roxane Pouliot
Int. J. Mol. Sci. 2024, 25(11), 5639; https://doi.org/10.3390/ijms25115639 - 22 May 2024
Viewed by 673
Abstract
Plaque psoriasis is a chronic inflammatory skin disease causing red inflamed lesions covered by scales. Leukocytes, including dendritic cells and T cells, participate in the inflammation of the skin by producing multiple cytokines, thus contributing to the hyperproliferation of keratinocytes. Lack of effectiveness [...] Read more.
Plaque psoriasis is a chronic inflammatory skin disease causing red inflamed lesions covered by scales. Leukocytes, including dendritic cells and T cells, participate in the inflammation of the skin by producing multiple cytokines, thus contributing to the hyperproliferation of keratinocytes. Lack of effectiveness and toxic side effects are the main concerns with conventional treatments, and research involving new antipsoriatic molecules is essential. In this study, the anti-inflammatory and antiproliferative effects of two natural polyphenols, phloretin and balsacone C, were investigated using the coculture of T cells and psoriatic keratinocytes. Phloretin exerted antiproliferative activity by regulating the expression of antigen Ki67 and proliferating cell nuclear antigen (PCNA). These effects were comparable to those of methotrexate, a reference treatment for moderate to severe psoriasis. With balsacone C, the expression of Ki67 was also reduced. Additionally, phloretin decreased the levels of multiple pro-inflammatory cytokines: monocyte chemoattractant protein-1 (MCP-1/CCL2), macrophage inflammatory protein-1α (MIP-1α), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-17A (IL-17A), and tumor necrosis factor alpha (TNF-α). The increased interleukin-2 (IL-2) levels with phloretin and methotrexate also represented anti-inflammatory activity. Balsacone C and methotrexate decreased the levels of IL-1α and IL-1β, but methotrexate exerted a higher reduction. In summary, the anti-inflammatory effects of phloretin were more pronounced than those of methotrexate and balsacone C. In addition, the expression of lymphocyte common antigen (CD45) was more similar to that of the healthy condition after using phloretin or methotrexate. Finally, phloretin stood out from the other compounds and appears promising for psoriasis treatment. Full article
(This article belongs to the Special Issue Psoriatic Arthritis and Skin Diseases: Pathogenesis and Therapies)
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13 pages, 4089 KiB  
Article
The Unknown Role of Periostin in Psoriatic Epidermal Hyperplasia
by Milena Wojciechowska, Kinga Ścibior, Monika Betyna-Białek, Ewa Kostrzewska and Oliwia McFarlane
Int. J. Mol. Sci. 2023, 24(22), 16295; https://doi.org/10.3390/ijms242216295 - 14 Nov 2023
Cited by 1 | Viewed by 1011
Abstract
Psoriasis is an inflammatory skin disease that affects 1–2% of the general population. The pathomechanism is based on type 1 immunological reactions. Hyperplasia of the epidermis in psoriasis is a result of disrupted epidermal architecture due to increased synthesis and expression of extracellular [...] Read more.
Psoriasis is an inflammatory skin disease that affects 1–2% of the general population. The pathomechanism is based on type 1 immunological reactions. Hyperplasia of the epidermis in psoriasis is a result of disrupted epidermal architecture due to increased synthesis and expression of extracellular matrix proteins. In our study, we analyzed the involvement of periostin (POSTN) in the pathogenesis of psoriasis, as one of the extracellular matrix proteins belonging to the fasciclin family. The study group consisted of 70 patients with psoriasis, while the control group comprised 30 healthy individuals. The serum concentrations of POSTN, Il-6, Il-17, Il-22, TNF-α and IFN-γ were measured in all participants. The severity of psoriasis was determined using the PASI (Psoriasis Area and Severity Index) score. The presence of POSTN in biopsy samples of 50 patients was assessed using the direct immunofluorescence method. The results were subjected to statistical analysis. The serum concentrations of POSTN, Il-6, Il-17, Il-22, TNF-α and IFN-γ in the study group are significantly higher than in the control group. Positive correlation has been demonstrated between the PASI score and the investigated cytokines, but not with POSTN. There was no statistically significant correlation between the POSTN level and the cytokines levels. POSTN deposits were localized in the epidermis in 66% of patients with psoriasis. The role of POSTN in the pathogenesis of psoriasis remains unclear. The mechanisms inducing the synthesis and expression of POSTN in psoriatic skin are not yet fully understood. Further research is needed to enhance our understanding of the mechanism underlying epidermal hyperplasia in psoriasis. Full article
(This article belongs to the Special Issue Psoriatic Arthritis and Skin Diseases: Pathogenesis and Therapies)
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13 pages, 1889 KiB  
Article
Dickkopf-Related Protein 1 (DKK-1) as a Possible Link between Bone Erosions and Increased Carotid Intima-Media Thickness in Psoriatic Arthritis: An Ultrasound Study
by Cristina-Elena Biță, Ștefan Cristian Dinescu, Anca-Lelia Riza, Paulina Lucia Ciurea, Anca Emanuela Mușetescu, Daniela Marinescu, Roxana Mihaela Dumitrașcu, Larisa Ionela Șuiu, Răzvan Adrian Ionescu, Horațiu Valeriu Popoviciu and Florentin Ananu Vreju
Int. J. Mol. Sci. 2023, 24(19), 14970; https://doi.org/10.3390/ijms241914970 - 7 Oct 2023
Viewed by 1253
Abstract
Psoriatic arthritis (PsA) is a heterogenous systemic inflammatory disorder that affects peripheral joints and skin, but also causes inflammation at entheseal sites, digits (dactylitis) and the axial skeleton. Despite considerable advances, our understanding of the pathogenesis and management of PsA is hampered by [...] Read more.
Psoriatic arthritis (PsA) is a heterogenous systemic inflammatory disorder that affects peripheral joints and skin, but also causes inflammation at entheseal sites, digits (dactylitis) and the axial skeleton. Despite considerable advances, our understanding of the pathogenesis and management of PsA is hampered by its complex clinical expression. We enrolled patients who met the ClASsification for Psoriatic Arthritis (CASPAR) criteria for PsA (n = 17), and healthy controls (n = 13). The lipid profile, C-reactive protein (CRP) and Dickkopf-related protein 1 (DKK-1) circulating levels were measured for all subjects. For the patients with PsA, (1) the erosive character of the articular disease was assessed by a musculoskeletal ultrasound and (2) the cardiovascular risk was evaluated using the Systematic Coronary Risk Evaluation (SCORE) chart and the ultrasound measurement of the carotid intima-media thickness. A higher titer of serum DKK-1 was associated with the presence of erosions (p < 0.005) and the cIMT correlated with DKK-1 levels in patients with PsA (r = 0.6356, p = 0.0061). Additionally, we observed a positive correlation between increased cIMT and CRP (r = 0.5186, p = 0.0329). Our results suggest that DKK-1 could be used as an early biomarker for the erosive character of the articular disease and for the assessment of the cardiovascular risk in PsA patients. Full article
(This article belongs to the Special Issue Psoriatic Arthritis and Skin Diseases: Pathogenesis and Therapies)
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12 pages, 1076 KiB  
Article
Crosstalk between Serum and Skin Sphingolipids in Psoriasis
by Mateusz Matwiejuk, Hanna Myśliwiec, Bartlomiej Lukaszuk, Marta Lewoc, Hend Malla, Piotr Myśliwiec, Jacek Dadan, Adrian Chabowski and Iwona Flisiak
Int. J. Mol. Sci. 2023, 24(19), 14872; https://doi.org/10.3390/ijms241914872 - 3 Oct 2023
Cited by 1 | Viewed by 947
Abstract
Psoriasis is a chronic, complex, immunological disorder, which may lead to many different systemic complications. Sphingolipids, including ceramide, are bioactive lipids, which take part in the regulation of immune reactions, cell growth, and apoptosis. Twenty psoriatic patients and twenty-eight control subjects were included [...] Read more.
Psoriasis is a chronic, complex, immunological disorder, which may lead to many different systemic complications. Sphingolipids, including ceramide, are bioactive lipids, which take part in the regulation of immune reactions, cell growth, and apoptosis. Twenty psoriatic patients and twenty-eight control subjects were included in the study. Skin (both lesional and non-lesional) and serum samples were collected from both the control group and the psoriatic patients. The levels of sphingosine (SFO), sphingosine-1-phosphate (S1P), sphingomyelin, sphinganine (SFA), sphinganine-1-phosphate (SFA1P), and ceramide (CER) were assessed in both tissue (t) and serum (s) samples using high-performance liquid chromatography (HPLC). We identified elevated serum levels of SFO, S1P, SFA, and SFA1P in psoriatic patients when compared to healthy individuals. As far as the lesional skin and serum of psoriatic patients are concerned, we demonstrated positive associations between CER_t and CER_s, SFA_t and CER_s, and SFO_t and CER_s. Additionally, we found negative correlations in the non-lesional skin and serum of psoriatic patients, including SFO_t vs. SFO_s, CER_t vs. SFA_s, CER_t vs. SFO_s, and SFO_t vs. SFA_s. Finally, we observed a positive correlation between S1P and SFA1P in both the serum samples of psoriatic patients and the serum samples of the control group. In this study, we did not observe any correlations between psoriasis area and severity index (PASI) scores and sphingolipid levels. In conclusion, our findings indicate an interplay between skin and serum lipids in psoriatic patients, which is not observed in healthy individuals. Full article
(This article belongs to the Special Issue Psoriatic Arthritis and Skin Diseases: Pathogenesis and Therapies)
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13 pages, 611 KiB  
Article
The IFIH1/MDA5 rs1990760 Gene Variant (946Thr) Differentiates Early- vs. Late-Onset Skin Disease and Increases the Risk of Arthritis in a Spanish Cohort of Psoriasis
by Pablo Coto-Segura, Daniel Vázquez-Coto, Lucinda Velázquez-Cuervo, Claudia García-Lago, Eliecer Coto and Rubén Queiro
Int. J. Mol. Sci. 2023, 24(19), 14803; https://doi.org/10.3390/ijms241914803 - 30 Sep 2023
Cited by 2 | Viewed by 1207
Abstract
The melanoma differentiation-associated protein 5 (MDA5; encoded by the IFIH1 gene) mediates the activation of the interferon pathway in response to a viral infection. This protein is also upregulated in autoimmune diseases and psoriasis skin lesions. IFIH1 gene variants that increase MDA5 activity [...] Read more.
The melanoma differentiation-associated protein 5 (MDA5; encoded by the IFIH1 gene) mediates the activation of the interferon pathway in response to a viral infection. This protein is also upregulated in autoimmune diseases and psoriasis skin lesions. IFIH1 gene variants that increase MDA5 activity have been associated with an increased risk for immune-mediated diseases, including psoriasis. Our aim is to determine the association between three IFIH1 variants (rs35337543 G/C, intron8 + 1; rs35744605 C/A, Glu627Stop; and rs1990760 C/T, Ala946Thr) and the main clinical findings in a cohort of Spanish patients with psoriasis (N = 572; 77% early-onset). Early-onset psoriasis patients (EOPs) had a significantly higher frequency of severe disease and the Cw6*0602 allele. Carriers of rs1990760 T (946Thr) were more common in the EOPs (p < 0.001), and the effect was more pronounced among Cw6*0602-negatives. This variant was also associated with an increased risk of psoriatic arthritis (PsA) independent from other factors (OR = 1.62, 95%CI = 1.11–2.37). The rs3533754 and rs35744605 polymorphisms did not show significant differences between the two onset age or PsA groups. Compared to the controls, the 946Thr variant was more common in the EOPs (nonsignificant difference) and significantly less common in patients aged >40 years (p = 0.005). In conclusion, the common IFIH1 rs1990760 T allele was significantly more frequent in early-onset compared to late-onset patients. This variant was also an independent risk factor for PsA in our cohort. Our study reinforces the widely reported role of the IFIH1 gene variants on psoriatic disease. Full article
(This article belongs to the Special Issue Psoriatic Arthritis and Skin Diseases: Pathogenesis and Therapies)
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17 pages, 1542 KiB  
Article
Transforming Psoriasis Care: Probiotics and Prebiotics as Novel Therapeutic Approaches
by Mihaela Cristina Buhaș, Rareș Candrea, Laura Ioana Gavrilaș, Doina Miere, Alexandru Tătaru, Andreea Boca and Adrian Cătinean
Int. J. Mol. Sci. 2023, 24(13), 11225; https://doi.org/10.3390/ijms241311225 - 7 Jul 2023
Cited by 9 | Viewed by 6163
Abstract
Psoriasis is a chronic inflammatory skin disease with autoimmune pathological characteristics. Recent research has found a link between psoriasis, inflammation, and gut microbiota dysbiosis, and that probiotics and prebiotics provide benefits to patients. This 12-week open-label, single-center clinical trial evaluated the efficacy of [...] Read more.
Psoriasis is a chronic inflammatory skin disease with autoimmune pathological characteristics. Recent research has found a link between psoriasis, inflammation, and gut microbiota dysbiosis, and that probiotics and prebiotics provide benefits to patients. This 12-week open-label, single-center clinical trial evaluated the efficacy of probiotics (Bacillus indicus (HU36), Bacillus subtilis (HU58), Bacillus coagulans (SC208), Bacillus licheniformis (SL307), and Bacillus clausii (SC109)) and precision prebiotics (fructooligosaccharides, xylooligosaccharides, and galactooligosaccharides) in patients with psoriasis receiving topical therapy, with an emphasis on potential metabolic, immunological, and gut microbiota changes. In total, 63 patients were evaluated, with the first 42 enrolled patients assigned to the intervention group and the next 21 assigned to the control group (2:1 ratio; non-randomized). There were between-group differences in several patient characteristics at baseline, including age, psoriasis severity (the incidence of severe psoriasis was greater in the intervention group than in the control group), the presence of nail psoriasis, and psoriatic arthritis, though it is not clear whether or how these differences may have affected the study findings. Patients with psoriasis receiving anti-psoriatic local therapy and probiotic and prebiotic supplementation performed better in measures of disease activity, including Psoriasis Area and Severity Index, Dermatology Life Quality Index, inflammatory markers, and skin thickness compared with those not receiving supplementation. Furthermore, in the 15/42 patients in the intervention group who received gut microbiota analysis, the gut microbiota changed favorably following 12 weeks of probiotic and prebiotic supplementation, with a shift towards an anti-inflammatory profile. Full article
(This article belongs to the Special Issue Psoriatic Arthritis and Skin Diseases: Pathogenesis and Therapies)
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