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Impaired Sphingomyelinase Activity and Epidermal Differentiation in Atopic Dermatitis
Open accessAbstract
A defective permeability barrier leads to the penetration of environmental allergens into the skin and initiates immunological reactions and inflammation crucially involved in the pathogenesis of atopic dermatitis (AD). Decreased stratum corneum ceramide content may cause the defect in permeability barrier function consistently found in AD. Acid and neutral sphingomyelinase (A- and N-SMase) generate ceramides with structural and signal transduction functions in epidermal proliferation and differentiation. We determined epidermal SMase activities, DNA synthesis, involucrin, loricrin, filaggrin, and keratin expression in lesional and non-lesional skin of AD patients. We found decreased epidermal A-SMase activity in lesional and non-lesional skin, correlating with reduced stratum corneum ceramide content and disturbed barrier function. N-SMase activity was reduced in non-lesional skin and more significantly reduced in lesional skin, correlating with impaired expression of cornified envelope proteins and keratins, important for skin barrier function. Changes in involucrin, loricrin, filaggrin, keratin K 5 (basal) and K 16 (proliferation associated) were noticed in non-lesional and lesional skin, whereas changes in K 10 (suprabasal), K 6 (proliferation associated), and K 17 (inflammation associated) were found only in lesional skin. In summary, reduction in SMase-generating ceramides and impaired differentiation are involved in the defective barrier function found in AD.
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“Atopic dry skin is associated with a marked reduction of skin barrier proteins, such as filaggrin (FLG) and loricrin (LOR).”
From Antioxidant Artemisia princeps Extract Enhances the Expression of Filaggrin and Loricrin via the AHR/OVOL1 Pathway (2017) · cites this paper as [12]
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“Skin inflammation decreases FLG and LOR expression and disrupts epidermal barrier function; moreover, in the opposite direction, barrier dysfunction augments skin inflammation [12,13,26].”
From Antioxidant Artemisia princeps Extract Enhances the Expression of Filaggrin and Loricrin via the AHR/OVOL1 Pathway (2017) · cites this paper as [12]
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Metadata
- Authors
- Jensen, J.-M., Fölster-Holst, R., Baranowsky, A., Schunck, M., Winoto-Morbach, S., Neumann, C., Schütze, S., & Proksch, E.
- Affiliations
- Christian-Albrechts-Universität zu Kiel (DE)
- Corresponding author
- Proksch, Ehrhardt
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2004-06
- Volume
- 122
- Issue
- 6
- Pages
- 1423-1431
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2077796802
- Cited by
- 309
- References
- 83
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 13 · 2023: 12 · 2022: 13 · 2021: 16 · 2020: 18 · 2019: 12 · 2018: 11 · 2017: 16 · 2016: 15 · 2015: 13 · 2014: 23 · 2013: 19 · 2012: 24
- FWCI
- 15.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 415)
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Keywords
- atopic dermatitis, sphingomyelinase, acid sphingomyelinase, neutral sphingomyelinase, ceramide, stratum corneum, skin barrier function, epidermal differentiation, involucrin, loricrin, filaggrin, keratin, DNA synthesis, lesional skin
- MeSH terms
- Filaggrin Proteins, Cell Differentiation, Cell Division, Ceramides, Dermatitis, Atopic, Epidermis, Female, Humans, Intermediate Filament Proteins, Keratins, Male, Membrane Proteins, Protein Precursors, Sphingomyelin Phosphodiesterase, Substrate Specificity, Water, Blotting, Western, Signal Transduction, Biomarkers
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