Improved organotypic skin model with reduced quantity of monounsaturated ceramides by inhibiting stearoyl-CoA desaturase-1

Helder, Richard W.J.; Rousel, Jannik; Boiten, Walter; Gooris, G.S.; Nădăban, Andreea; Ghalbzouri, Abdoelwaheb El; Bouwstra, Joke A.

doi:10.1016/j.bbalip.2021.158885

Cited by 6 publications

(8 citation statements)

References 39 publications

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“…All together these changes led to the formation of an altered lamellar organization and a reduced lipid packing density. The repeat distance of the LPP is shorter in HSEs than that in NHS and no SPP could be detected in HSEs 19 . Furthermore, most of the lipids form a hexagonal packing rather than a predominantly orthorhombic packing as observed in NHS.…”

Section: Introductionmentioning

confidence: 79%

“…The repeat distance of the LPP is shorter in HSEs than that in NHS and no SPP could be detected in HSEs. 19 Furthermore, most of the lipids form a hexagonal packing rather than a predominantly orthorhombic packing as observed in NHS. Ultimately, these changes in lipid composition and subsequent lipid organization may contribute to a reduced skin barrier.…”

Section: Introductionmentioning

confidence: 98%

“…17,18,[20][21][22][23] In order to improve the lipid composition of HSEs, recent studies demonstrated valuable improvements in HSEs by (down) regulating enzymes or receptors involved in the lipid synthesis. 16,19 These studies focused on the reduction of a key enzyme that is overexpressed in HSEs, which is stearoyl-CoA desaturase-1 (SCD1). [24][25][26] was targeted by using a small molecule inhibitor of the enzyme, 19 or by deactivation of the liver X receptor.…”

Section: Introductionmentioning

confidence: 99%

“…16,19 These studies focused on the reduction of a key enzyme that is overexpressed in HSEs, which is stearoyl-CoA desaturase-1 (SCD1). [24][25][26] was targeted by using a small molecule inhibitor of the enzyme, 19 or by deactivation of the liver X receptor. 16 These studies demonstrated that reducing SCD1 activity has great potential in normalizing the lipid synthesis in HSEs and subsequently improving the lipid organization.…”

Section: Introductionmentioning

confidence: 99%

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The effect of PPAR isoform (de)activation on the lipid composition in full‐thickness skin models

Helder

Rousel

Boiten

et al. 2023

Experimental Dermatology

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Human skin equivalents (HSEs) are 3D-cultured human skin models that mimic many aspects of native human skin (NHS). Although HSEs resemble NHS very closely, the barrier located in the stratum corneum (SC) is impaired. This is caused by an altered lipid composition in the SC of HSEs compared with NHS. One of the most pronounced changes in this lipid composition is a high level of monounsaturation. One key enzyme in this change is stearoyl-CoA desaturase-1 (SCD1), which catalyses the monounsaturation of lipids. In order to normalize the lipid composition, we aimed to target a group of nuclear receptors that are important regulators in the lipid synthesis. This group of receptors are known as the peroxisome proliferating activating receptors (PPARs). By (de)activating each isoform (PPARα, PPARδ and PPARγ), the PPAR isoforms may have normalizing effects on the lipid composition. In addition, another PPARα agonist Wy14643 was included as this supplement demonstrated normalizing effects in the lipid composition in a more recent study. After PPAR (ant)agonists supplementation, the mRNA of downstream targets, lipid synthesis genes and lipid composition were investigated. The PPAR downstream targets were activated, indicating that the supplements reached the keratinocytes to trigger their effect. However, minimal impact was observed on the lipid composition after PPAR isoform (de) activation. Only the highest concentration Wy14643 resulted in strong, but negative effects on CER composition. Although the novel tested modifications did not result in an improvement, more insight is gained on the nuclear receptors PPARs and their effects on the lipid barrier in full-thickness skin models.

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Section: Introductionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The effect of PPAR isoform (de)activation on the lipid composition in full‐thickness skin models

Helder

Rousel

Boiten

et al. 2023

Experimental Dermatology

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show abstract

“…The time spent at the air–liquid interface during our study is similar to the time needed for the epidermis to completely form in NHS, a duration that can also be found in other studies using different types of dermal compartments [ 33 , 34 ]. Some models can be found in the literature, however, where culture conditions were adjusted for a shorter duration at the air–liquid interface of 14 to 17 days [ 35 , 36 , 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Docosahexaenoic Acid Modulates Paracellular Absorption of Testosterone and Claudin-1 Expression in a Tissue-Engineered Skin Model

Tremblay

Simard

Morin

et al. 2021

IJMS

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Healthy skin moLEdels produced by tissue-engineering often present a suboptimal skin barrier function as compared with normal human skin. Moreover, skin substitutes reconstructed according to the self-assembly method were found to be deficient in polyunsaturated fatty acids (PUFAs). Therefore, in this study, we investigated the effects of a supplementation of the culture media with docosahexaenoic acid (DHA) on the barrier function of skin substitutes. To this end, 10 μM DHA-supplemented skin substitutes were produced (n = 3), analyzed, and compared with controls (substitutes without supplementation). A Franz cell diffusion system, followed by ultra-performance liquid chromatography, was used to perform a skin permeability to testosterone assay. We then used gas chromatography to quantify the PUFAs found in the epidermal phospholipid fraction of the skin substitutes, which showed successful DHA incorporation. The permeability to testosterone was decreased following DHA supplementation and the lipid profile was improved. Differences in the expression of the tight junction (TJ) proteins claudin-1, claudin-4, occludin, and TJ protein-1 were observed, principally a significant increase in claudin-1 expression, which was furthermore confirmed by Western blot analyses. In conclusion, these results confirm that the DHA supplementation of cell culture media modulates different aspects of skin barrier function in vitro and reflects the importance of n-3 PUFAs regarding the lipid metabolism in keratinocytes.

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Human skin equivalents: Impaired barrier function in relation to the lipid and protein properties of the stratum corneum

Bouwstra

Helder

Ghalbzouri

2021

Advanced Drug Delivery Reviews

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Improved organotypic skin model with reduced quantity of monounsaturated ceramides by inhibiting stearoyl-CoA desaturase-1

Cited by 6 publications

References 39 publications

The effect of PPAR isoform (de)activation on the lipid composition in full‐thickness skin models

The effect of PPAR isoform (de)activation on the lipid composition in full‐thickness skin models

Docosahexaenoic Acid Modulates Paracellular Absorption of Testosterone and Claudin-1 Expression in a Tissue-Engineered Skin Model

Human skin equivalents: Impaired barrier function in relation to the lipid and protein properties of the stratum corneum

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