Skin Barrier Dysregulation in Psoriasis

Andreas, Orsmond; Bereza-Malcolm, Lara; Lynch, T Sean; March, Lyn; Xue, Meilang

doi:10.3390/ijms221910841

Cited by 94 publications

(58 citation statements)

References 268 publications

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“…PTPμ interacts with vascular endothelial (VE)-cadherin and regulates both the tyrosine phosphorylation state of VE-cadherin and the integrity of the barrier function [ 60 ]. In a similar perspective, these results can be extrapolated to psoriatic skin, which is also characterized by an impaired epidermal barrier function [ 61 , 62 , 63 ]. PTPμ is also known to interact with other classical cadherins, including epithelial (E-) cadherin [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Gene Profiling of a 3D Psoriatic Skin Model Enriched in T Cells: Downregulation of PTPRM Promotes Keratinocyte Proliferation through Excessive ERK1/2 Signaling

Rioux

Turgeon

Le‐Bel

et al. 2022

Cells

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Psoriasis is a complex, immune-mediated skin disease involving a wide range of epithelial and immune cells. The underlying mechanisms that govern the epidermal defects and immunological dysfunction observed in this condition remain largely unknown. In recent years, the emergence of new, more sophisticated models has allowed the evolution of our knowledge of the pathogenesis of psoriasis. The development of psoriatic skin biomaterials that more closely mimic native psoriatic skin provides advanced preclinical models that will prove relevant in predicting clinical outcomes. In this study, we used a tissue-engineered, two-layered (dermis and epidermis) human skin substitute enriched in T cells as a biomaterial to study both the cellular and molecular mechanisms involved in psoriasis’ pathogenesis. Gene profiling on microarrays revealed significant changes in the profile of genes expressed by the psoriatic skin substitutes compared with the healthy ones. Two genes, namely, PTPRM and NELL2, whose products influence the ERK1/2 signaling pathway have been identified as being deregulated in psoriatic substitutes. Deregulation of these genes supports excessive activation of the ERK1/2 pathway in psoriatic skin substitutes. Most importantly, electrophoresis mobility shift assays provided evidence that the DNA-binding properties of two downstream nuclear targets of ERK1/2, both the NF-κB and Sp1 transcription factors, are increased under psoriatic conditions. Moreover, the results obtained with the inhibition of RSK, a downstream effector of ERK1/2, supported the therapeutic potential of inhibiting this signaling pathway for psoriasis treatment. In conclusion, this two-layered human psoriatic skin substitute enriched in T cells may prove particularly useful in deciphering the mechanistic details of psoriatic pathogenesis and provide a relevant biomaterial for the study of potential therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Gene Profiling of a 3D Psoriatic Skin Model Enriched in T Cells: Downregulation of PTPRM Promotes Keratinocyte Proliferation through Excessive ERK1/2 Signaling

Rioux

Turgeon

Le‐Bel

et al. 2022

Cells

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“…As the histological analysis of recovering human and mouse wounds indicated that OLFM4 was induced at the proliferative phase of wound healing, we next sought to investigate whether its expression pattern was altered in skin disorders. Psoriasis is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation [ 25 ] and is accompanied by accelerated wound healing [ 26 ]. Examination of OLFM4 expression in psoriatic lesional skin showed increased levels of the protein in epidermis compared to healthy skin (Fig.…”

Section: Resultsmentioning

confidence: 99%

Olfactomedin-4 improves cutaneous wound healing by promoting skin cell proliferation and migration through POU5F1/OCT4 and ESR1 signalling cascades

Klaas

Mäemets-Allas

Heinmäe

et al. 2022

Cell. Mol. Life Sci.

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Olfactomedin-4 (OLFM4) is an olfactomedin-domain-containing glycoprotein, which regulates cell adhesion, proliferation, gastrointestinal inflammation, innate immunity and cancer metastasis. In the present study we investigated its role in skin regeneration. We found that OLFM4 expression is transiently upregulated in the proliferative phase of cutaneous wound healing in humans as well as in mice. Moreover, a significant increase in OLFM4 expression was detected in the skin of lesional psoriasis, a chronic inflammatory disease characterized by keratinocyte hyperproliferation. In vitro experiments demonstrated that OLFM4 selectively stimulated keratinocyte proliferation and increased both keratinocyte and fibroblast migration. Using proteotranscriptomic pathway analysis we revealed that transcription factors POU5F1/OCT4 and ESR1 acted as hubs for OLFM4-induced signalling in keratinocytes. In vivo experiments utilizing mouse splinted full-thickness cutaneous wound healing model showed that application of recombinant OLFM4 protein can significantly improve wound healing efficacy. Taken together, our results suggest that OLFM4 acts as a transiently upregulated inflammatory signal that promotes wound healing by regulating both dermal and epidermal cell compartments of the skin.

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“…Hyperproliferation with altered-differentiation of keratinocytes are the main characteristics of psoriasis [ 37 ]. The disrupted skin barrier promotes subsequent immune dysfunction, which contributes to the maintenance of inflammatory skin microenvironment of psoriasis [ 38 ]. To determine whether AEC-SC or UMSC-SC affect the integrity of skin barrier, we investigated the proliferation and differentiation of keratinocytes.…”

Section: Resultsmentioning

confidence: 99%

Topical administration of the secretome derived from human amniotic epithelial cells ameliorates psoriasis-like skin lesions in mice

et al. 2022

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Background Psoriasis is a chronic inflammatory skin disease. Tissue stem cells have exhibited a therapeutic effect on psoriatic mice. However, the therapeutic effect of topical administration of the secretome derived from tissue stem cells on psoriasis has not been reported. Methods The secretome from human amniotic epithelial cells (AEC-SC) and human umbilical cord mesenchymal stem cells (UMSC-SC) was topically administrated on the back of imiquimod-induced psoriasis-like mice. Subsequently, we observed the skin lesions and skin inflammation of psoriasis-like mice. Next, we further analyzed the paracrine factors in AEC-SC and UMSC-SC by protein chips. Lastly, the effect of the crucial paracrine factor was investigated by imiquimod-induced psoriasis-like mice. Results We found that AEC-SC had a better therapeutic effect on attenuating psoriasis-like skin lesions including skin scales, skin redness and skin thickness than UMSC-SC, and it had a better regulatory effect on keratinocyte hyperproliferation and altered differentiation. Thus, we focused on AEC-SC. Further study showed that AEC-SC reduced the infiltration of neutrophils and interleukin-17-producing T cells. Next, the analysis of AEC-SC with protein chip revealed that the levels of anti-inflammatory factor interleukin-1 receptor antagonist (IL-1ra) were much higher in AEC-SC compared to that in UMSC-SC. More importantly, the beneficial effect of AEC-SC on psoriasis-like skin lesions and skin inflammation of mice were significantly impaired when neutralizing with IL-1ra antibody, while the recombinant human IL-1ra showed a less protective effect than AEC-SC. Conclusions The present study demonstrated that AEC-SC could efficiently ameliorate psoriasis-like skin lesions and skin inflammation and IL-1ra plays an essential role. Therefore, topical administration of AEC-SC may provide a novel strategy for treating psoriasis-like inflammatory skin diseases.

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Skin Barrier Dysregulation in Psoriasis

Cited by 94 publications

References 268 publications

Gene Profiling of a 3D Psoriatic Skin Model Enriched in T Cells: Downregulation of PTPRM Promotes Keratinocyte Proliferation through Excessive ERK1/2 Signaling

Gene Profiling of a 3D Psoriatic Skin Model Enriched in T Cells: Downregulation of PTPRM Promotes Keratinocyte Proliferation through Excessive ERK1/2 Signaling

Olfactomedin-4 improves cutaneous wound healing by promoting skin cell proliferation and migration through POU5F1/OCT4 and ESR1 signalling cascades

Topical administration of the secretome derived from human amniotic epithelial cells ameliorates psoriasis-like skin lesions in mice

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