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Disruption of the Sjögren-Larsson Syndrome Gene Aldh3a2 in Mice Increases Keratinocyte Growth and Retards Skin Barrier Recovery
- Source :
- Journal of Biological Chemistry. 291:11676-11688
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- The fatty aldehyde dehydrogenase (FALDH) ALDH3A2 is the causative gene of Sjogren Larsson syndrome (SLS). To date, the molecular mechanism underlying the symptoms characterizing SLS has been poorly understood. Using Aldh3a2(-/-) mice, we found here that Aldh3a2 was the major FALDH active in undifferentiated keratinocytes. Long-chain base metabolism was greatly impaired in Aldh3a2(-/-) keratinocytes. Phenotypically, the intercellular spaces were widened in the basal layer of the Aldh3a2(-/-) epidermis due to hyperproliferation of keratinocytes. Furthermore, oxidative stress-induced genes were upregulated in Aldh3a2(-/-) keratinocytes. Upon keratinocyte differentiation, the activity of another FALDH, Aldh3b2, surpassed that of Aldh3a2. As a result, Aldh3a2(-/-) mice were indistinguishable from wild-type mice in terms of their whole epidermis FALDH activity, and their skin barrier function was uncompromised under normal conditions. However, perturbation of the stratum corneum caused increased transepidermal water loss and delayed barrier recovery in Aldh3a2(-/-) mice. In conclusion, Aldh3a2(-/-) mice replicated some aspects of SLS symptoms, especially at the basal layer of the epidermis. Our results suggest that hyperproliferation of keratinocytes via oxidative stress responses may partly contribute to the ichthyosis symptoms of SLS.
- Subjects :
- Keratinocytes
Male
0301 basic medicine
Ceramide
Cell Membrane Permeability
Blotting, Western
Apoptosis
Biology
Real-Time Polymerase Chain Reaction
medicine.disease_cause
Biochemistry
Mice
03 medical and health sciences
chemistry.chemical_compound
medicine
Stratum corneum
Animals
RNA, Messenger
Molecular Biology
Cells, Cultured
Gene knockout
Cell Proliferation
Skin
Mice, Knockout
Transepidermal water loss
Sjögren–Larsson syndrome
integumentary system
Reverse Transcriptase Polymerase Chain Reaction
Ichthyosis
Cell Biology
medicine.disease
Aldehyde Oxidoreductases
Molecular biology
Mice, Inbred C57BL
Sjogren-Larsson Syndrome
Metabolism
030104 developmental biology
medicine.anatomical_structure
chemistry
Immunology
Female
Keratinocyte
Oxidative stress
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 291
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....6e0d160611a61900bb38719ae008391a