Remodeling of the Dermal Extracellular Matrix in a Tissue-Engineered Psoriatic Skin Model by n-3 Polyunsaturated Fatty Acids
Psoriasis is an inflammatory skin disease mainly associated with an epidermal disorder. However, the involvement of the dermal extracellular matrix (ECM) composition in psoriasis is still poorly understood. This study aimed to investigate the expression of ECM components in psoriatic skin substitute...
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| Format: | Article |
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MDPI AG
2022-05-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/5/1078 |
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| author | Mélissa Simard Alexe Grenier Geneviève Rioux Andréa Tremblay Isalie Blais Nicolas Flamand Roxane Pouliot |
| author_facet | Mélissa Simard Alexe Grenier Geneviève Rioux Andréa Tremblay Isalie Blais Nicolas Flamand Roxane Pouliot |
| author_sort | Mélissa Simard |
| collection | DOAJ |
| description | Psoriasis is an inflammatory skin disease mainly associated with an epidermal disorder. However, the involvement of the dermal extracellular matrix (ECM) composition in psoriasis is still poorly understood. This study aimed to investigate the expression of ECM components in psoriatic skin substitutes (PS<sup>−</sup>) compared with healthy skin substitutes (HS<sup>−</sup>), as well as the effect of an n-3 polyunsaturated fatty acid, namely α-linolenic acid (ALA), on the psoriatic dermal compartment (PS<sup>ALA+</sup>). Liquid chromatography tandem mass spectrometry analyses revealed that the lipidome of PS<sup>−</sup> contained higher amounts of n-6 derived prostaglandins (PGE<sub>2</sub>) and lipoxygenase products (9-HODE and 15-HETE). ALA supplementation increased the levels of PGE<sub>3</sub>, 13-HOTrE, 15-HEPE, and 18-HEPE, and decreased the levels of PGE<sub>2</sub>, 15-HETE, and 9-HOPE compared with PS<sup>−</sup>, indicating that ALA modulates the dermal lipidome of psoriatic skin substitutes. Gene expression profiling showed that several genes encoding for different ECM proteins were overexpressed in PS<sup>−</sup> compared with HS<sup>−</sup>, namely <i>COL1A1</i> (4.2-fold), <i>COL1A2</i> (3-fold), <i>COL3A1</i> (4.4-fold), <i>COL4A1</i> (2.3-fold), <i>COL4A2</i> (6.3-fold), <i>COL5A1</i> (3.3-fold), <i>COL5A2</i> (5.2-fold), and <i>COL5A3</i> (4.6-fold). Moreover, the expression of collagen IV (Col IV), collagen VII (Col VII), and laminin was found to be increased in PS<sup>−</sup> compared with HS<sup>−</sup>, and to be restored with ALA (PS<sup>ALA+</sup>) according to immunofluorescence staining, while only the collagen I to collagen III ratio was altered according to dot blot analyses. Linear regression analysis revealed several positive correlations, including Col III with 14-HDHA levels, fibronectin with 12-HETE and 15-HETE levels, the dermo-epidermal junction Col IV with PGF<sub>2</sub><sub>α</sub>, 9-HODE, and 13-HODE levels, and laminin with levels of PGF<sub>2</sub><sub>α</sub>, 9-HODE, 13-HODE, 5-HETE, 12-HETE, and 15-HETE. These results suggest that the ECM plays an underestimated role in the pathogenesis of psoriasis and that ALA supplementation can regulate the ECM composition. |
| first_indexed | 2024-03-10T03:17:35Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-10T03:17:35Z |
| publishDate | 2022-05-01 |
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| series | Biomedicines |
| spelling | doaj.art-87ed6d12cb774a38a75279b598a98fda2023-11-23T10:10:45ZengMDPI AGBiomedicines2227-90592022-05-01105107810.3390/biomedicines10051078Remodeling of the Dermal Extracellular Matrix in a Tissue-Engineered Psoriatic Skin Model by n-3 Polyunsaturated Fatty AcidsMélissa Simard0Alexe Grenier1Geneviève Rioux2Andréa Tremblay3Isalie Blais4Nicolas Flamand5Roxane Pouliot6Centre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1J 1Z4, CanadaCentre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1J 1Z4, CanadaCentre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1J 1Z4, CanadaCentre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1J 1Z4, CanadaCentre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1J 1Z4, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Département de Médecine, Faculté de Médecine, Université Laval, Québec, QC G1V 4G5, CanadaCentre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1J 1Z4, CanadaPsoriasis is an inflammatory skin disease mainly associated with an epidermal disorder. However, the involvement of the dermal extracellular matrix (ECM) composition in psoriasis is still poorly understood. This study aimed to investigate the expression of ECM components in psoriatic skin substitutes (PS<sup>−</sup>) compared with healthy skin substitutes (HS<sup>−</sup>), as well as the effect of an n-3 polyunsaturated fatty acid, namely α-linolenic acid (ALA), on the psoriatic dermal compartment (PS<sup>ALA+</sup>). Liquid chromatography tandem mass spectrometry analyses revealed that the lipidome of PS<sup>−</sup> contained higher amounts of n-6 derived prostaglandins (PGE<sub>2</sub>) and lipoxygenase products (9-HODE and 15-HETE). ALA supplementation increased the levels of PGE<sub>3</sub>, 13-HOTrE, 15-HEPE, and 18-HEPE, and decreased the levels of PGE<sub>2</sub>, 15-HETE, and 9-HOPE compared with PS<sup>−</sup>, indicating that ALA modulates the dermal lipidome of psoriatic skin substitutes. Gene expression profiling showed that several genes encoding for different ECM proteins were overexpressed in PS<sup>−</sup> compared with HS<sup>−</sup>, namely <i>COL1A1</i> (4.2-fold), <i>COL1A2</i> (3-fold), <i>COL3A1</i> (4.4-fold), <i>COL4A1</i> (2.3-fold), <i>COL4A2</i> (6.3-fold), <i>COL5A1</i> (3.3-fold), <i>COL5A2</i> (5.2-fold), and <i>COL5A3</i> (4.6-fold). Moreover, the expression of collagen IV (Col IV), collagen VII (Col VII), and laminin was found to be increased in PS<sup>−</sup> compared with HS<sup>−</sup>, and to be restored with ALA (PS<sup>ALA+</sup>) according to immunofluorescence staining, while only the collagen I to collagen III ratio was altered according to dot blot analyses. Linear regression analysis revealed several positive correlations, including Col III with 14-HDHA levels, fibronectin with 12-HETE and 15-HETE levels, the dermo-epidermal junction Col IV with PGF<sub>2</sub><sub>α</sub>, 9-HODE, and 13-HODE levels, and laminin with levels of PGF<sub>2</sub><sub>α</sub>, 9-HODE, 13-HODE, 5-HETE, 12-HETE, and 15-HETE. These results suggest that the ECM plays an underestimated role in the pathogenesis of psoriasis and that ALA supplementation can regulate the ECM composition.https://www.mdpi.com/2227-9059/10/5/1078psoriasisinflammatory diseasen-3 PUFAalpha-linolenic acidbioactive lipid mediatorsextracellular matrix |
| spellingShingle | Mélissa Simard Alexe Grenier Geneviève Rioux Andréa Tremblay Isalie Blais Nicolas Flamand Roxane Pouliot Remodeling of the Dermal Extracellular Matrix in a Tissue-Engineered Psoriatic Skin Model by n-3 Polyunsaturated Fatty Acids Biomedicines psoriasis inflammatory disease n-3 PUFA alpha-linolenic acid bioactive lipid mediators extracellular matrix |
| title | Remodeling of the Dermal Extracellular Matrix in a Tissue-Engineered Psoriatic Skin Model by n-3 Polyunsaturated Fatty Acids |
| title_full | Remodeling of the Dermal Extracellular Matrix in a Tissue-Engineered Psoriatic Skin Model by n-3 Polyunsaturated Fatty Acids |
| title_fullStr | Remodeling of the Dermal Extracellular Matrix in a Tissue-Engineered Psoriatic Skin Model by n-3 Polyunsaturated Fatty Acids |
| title_full_unstemmed | Remodeling of the Dermal Extracellular Matrix in a Tissue-Engineered Psoriatic Skin Model by n-3 Polyunsaturated Fatty Acids |
| title_short | Remodeling of the Dermal Extracellular Matrix in a Tissue-Engineered Psoriatic Skin Model by n-3 Polyunsaturated Fatty Acids |
| title_sort | remodeling of the dermal extracellular matrix in a tissue engineered psoriatic skin model by n 3 polyunsaturated fatty acids |
| topic | psoriasis inflammatory disease n-3 PUFA alpha-linolenic acid bioactive lipid mediators extracellular matrix |
| url | https://www.mdpi.com/2227-9059/10/5/1078 |
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