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The effects of LXR agonist T0901317 and LXR antagonist GSK2033 on morphogenesis and lipid properties in full thickness skin models
- Source :
- Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids, Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids, 1865(2), 158546, 'Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids ', vol: 1865, pages: 158546-1-158546-10 (2020)
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Full thickness models (FTMs) are 3D-cultured human skin models that mimic many aspects of native human skin (NHS). However, their stratum corneum (SC) lipid composition differs from NHS causing a reduced skin barrier. The most pronounced differences in lipid composition are a reduction in lipid chain length and increased monounsaturated lipids. The liver-X-receptor (LXR) activates the monounsaturated lipid synthesis via stearoyl-CoA desaturase-1 (SCD-1). Therefore, the aim was to improve the SC lipid synthesis of FTMs by LXR deactivation. This was achieved by supplementing culture medium with LXR antagonist GSK2033. LXR agonist T0901317 was added for comparison. Subsequently, epidermal morphogenesis, lipid composition, lipid organization and the barrier functionality of these FTMs were assessed. We demonstrate that LXR deactivation resulted in a lipid composition with increased overall chain lengths and reduced levels of monounsaturation, whereas LXR activation increased the amount of monounsaturated lipids and led to a reduction in the overall chain length. However, these changes did not affect the barrier functionality. In conclusion, LXR deactivation led to the development of FTMs with improved lipid properties, which mimic the lipid composition of NHS more closely. These novel findings may contribute to design interventions to normalize SC lipid composition of atopic dermatitis patients.
- Subjects :
- 0301 basic medicine
Agonist
medicine.medical_specialty
Hydrocarbons, Fluorinated
medicine.drug_class
Primary Cell Culture
Drug Evaluation, Preclinical
Morphogenesis
Human skin
Fatty Acids, Nonesterified
Ceramides
Free fatty acids
Dermatitis, Atopic
03 medical and health sciences
Nuclear receptors/LXR
0302 clinical medicine
Internal medicine
Stratum corneum
medicine
Full thickness skin
Humans
Liver X receptor
Molecular Biology
Liver X Receptors
Skin
Atopic dermatitis
Sulfonamides
Chemistry
Lipogenesis
Antagonist
Lipid metabolism
Cell Biology
Culture Media
Stearoyl-CoA desaturase
Monounsaturated
030104 developmental biology
medicine.anatomical_structure
Endocrinology
030220 oncology & carcinogenesis
lipids (amino acids, peptides, and proteins)
Subjects
Details
- ISSN :
- 13881981
- Volume :
- 1865
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
- Accession number :
- edsair.doi.dedup.....8f5609c28e80c4ce55a8626b089c99b9
- Full Text :
- https://doi.org/10.1016/j.bbalip.2019.158546