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ARNT mice controlling skin function?

Junji Takeda and colleagues from Osaka University and the National Cancer Institute reveal that the aryl hydrocarbon receptor nuclear translocator (ARNT) affects the structure of ceramides in the skin and disrupts the function of the epidermal barrier, which protects against foreign environmental stimuli and injury. These findings are reported in the November 3 issue of the Journal of Clinical Investigation.

ARNT, a transcription factor of the Per/AHR/ARNT/Sim family, regulates gene expression in response to environmental stimuli such as xenobiotics and hypoxia. To examine its role in the epidermis, Takeda and colleagues disrupted Arnt in keratinocytes. While the architecture of the stratum corneum in Arnt/ mice was found to be similar to that in control mice, the permeability barrier function and the composition of ceramides were significantly different. In particular, 4-desaturated and 4-hydroxylated ceramide species were diminished in the Arnt/ mice, whereas 4-saturated ceramides were elevated.

These data suggest that ARNT regulates ceramide biosynthesis through 4-desaturation and that maintenance of ceramide composition is important in epithelial barrier function.

TITLE: Alteration of the 4-sphingenine scaffolds of ceramides in keratinocyte-specific Arnt-deficient mice affects skin barrier function

AUTHOR CONTACT:
Junji Takeda
Osaka University Graduate School of Medicine, Osaka, Japan.
Phone: 81-6-6879-3262
Fax: 81-6-6879-3266
E-mail: takeda@mr-en
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Contact: Brooke Grindlinger
science_editor@the-jci.org
212-342-9006
Journal of Clinical Investigation
3-Nov-2003