N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model
Abstract Psoriasis is an inflammatory skin disease that is characterized by keratinocyte hyperproliferation, abnormal epidermal differentiation and dysregulated lipid metabolism. Some lipid mediators of the N-acylethanolamines (NAEs) and monoacylglycerols (MAGs) can bind to cannabinoid (CB) receptor...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-39185-4 |
| _version_ | 1827890439677542400 |
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| author | Mélissa Simard Andréa Tremblay Sophie Morin Geneviève Rioux Nicolas Flamand Roxane Pouliot |
| author_facet | Mélissa Simard Andréa Tremblay Sophie Morin Geneviève Rioux Nicolas Flamand Roxane Pouliot |
| author_sort | Mélissa Simard |
| collection | DOAJ |
| description | Abstract Psoriasis is an inflammatory skin disease that is characterized by keratinocyte hyperproliferation, abnormal epidermal differentiation and dysregulated lipid metabolism. Some lipid mediators of the N-acylethanolamines (NAEs) and monoacylglycerols (MAGs) can bind to cannabinoid (CB) receptors and are referred to as part of the endocannabinoidome. Their implication in psoriasis remains unknown. The aim of the present study was to characterize the endocannabinoid system and evaluate the effects of n-3-derived NAEs, namely N-eicosapentaenoyl-ethanolamine (EPEA), in psoriatic keratinocytes using a psoriatic skin model produced by tissue engineering, following the self-assembly method. Psoriatic skin substitutes had lower FAAH2 expression and higher MAGL, ABHD6 and ABHD12 expression compared with healthy skin substitutes. Treatments with alpha-linolenic acid (ALA) increased the levels of EPEA and 1/2-docosapentaenoyl-glycerol, showing that levels of n-3 polyunsaturated fatty acids modulate related NAE and MAG levels. Treatments of the psoriatic substitutes with 10 μM of EPEA for 7 days resulted in decreased epidermal thickness and number of Ki67 positive keratinocytes, both indicating decreased proliferation of psoriatic keratinocytes. EPEA effects on keratinocyte proliferation were inhibited by the CB1 receptor antagonist rimonabant. Exogenous EPEA also diminished some inflammatory features of psoriasis. In summary, n-3-derived NAEs can reduce the psoriatic phenotype of a reconstructed psoriatic skin model. |
| first_indexed | 2024-03-12T21:09:45Z |
| format | Article |
| id | doaj.art-25106353a77644fc9aa43d886a4aedf2 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T21:09:45Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-25106353a77644fc9aa43d886a4aedf22023-07-30T11:13:00ZengNature PortfolioScientific Reports2045-23222023-07-0113111210.1038/s41598-023-39185-4N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin modelMélissa Simard0Andréa Tremblay1Sophie Morin2Geneviève Rioux3Nicolas Flamand4Roxane Pouliot5Centre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, Axe médecine régénératrice, Centre de recherche du CHU de Québec-Université LavalCentre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, Axe médecine régénératrice, Centre de recherche du CHU de Québec-Université LavalCentre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, Axe médecine régénératrice, Centre de recherche du CHU de Québec-Université LavalCentre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, Axe médecine régénératrice, Centre de recherche du CHU de Québec-Université LavalCentre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Département de médecine, Faculté de médecine, Université LavalCentre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, Axe médecine régénératrice, Centre de recherche du CHU de Québec-Université LavalAbstract Psoriasis is an inflammatory skin disease that is characterized by keratinocyte hyperproliferation, abnormal epidermal differentiation and dysregulated lipid metabolism. Some lipid mediators of the N-acylethanolamines (NAEs) and monoacylglycerols (MAGs) can bind to cannabinoid (CB) receptors and are referred to as part of the endocannabinoidome. Their implication in psoriasis remains unknown. The aim of the present study was to characterize the endocannabinoid system and evaluate the effects of n-3-derived NAEs, namely N-eicosapentaenoyl-ethanolamine (EPEA), in psoriatic keratinocytes using a psoriatic skin model produced by tissue engineering, following the self-assembly method. Psoriatic skin substitutes had lower FAAH2 expression and higher MAGL, ABHD6 and ABHD12 expression compared with healthy skin substitutes. Treatments with alpha-linolenic acid (ALA) increased the levels of EPEA and 1/2-docosapentaenoyl-glycerol, showing that levels of n-3 polyunsaturated fatty acids modulate related NAE and MAG levels. Treatments of the psoriatic substitutes with 10 μM of EPEA for 7 days resulted in decreased epidermal thickness and number of Ki67 positive keratinocytes, both indicating decreased proliferation of psoriatic keratinocytes. EPEA effects on keratinocyte proliferation were inhibited by the CB1 receptor antagonist rimonabant. Exogenous EPEA also diminished some inflammatory features of psoriasis. In summary, n-3-derived NAEs can reduce the psoriatic phenotype of a reconstructed psoriatic skin model.https://doi.org/10.1038/s41598-023-39185-4 |
| spellingShingle | Mélissa Simard Andréa Tremblay Sophie Morin Geneviève Rioux Nicolas Flamand Roxane Pouliot N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model Scientific Reports |
| title | N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model |
| title_full | N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model |
| title_fullStr | N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model |
| title_full_unstemmed | N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model |
| title_short | N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model |
| title_sort | n eicosapentaenoyl ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model |
| url | https://doi.org/10.1038/s41598-023-39185-4 |
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