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Ceramides stimulate caspase-14 expression in human keratinocytes
Yan J Jiang1, Peggy Kim, Yoshikazu Uchida
1Metabolism Section, Veterans Affairs Medical Center, Northern California Institute for Research and Education, University of California at San Francisco, San Francisco, CA 94121, USA. yan.jiang@med.va.gov
Experimental Dermatology
|February 1, 2013
Summary
Ceramides stimulate the expression of caspase-14 (an enzyme crucial for skin cell differentiation) in human keratinocytes. This finding reveals a novel regulatory mechanism for skin barrier formation.
Area of Science:
- Biochemistry
- Dermatology
- Molecular Biology
Background:
- Caspase-14 is predominantly expressed in cornifying epithelia.
- It plays a key role in the terminal differentiation of keratinocytes.
- Regulation of caspase-14 expression is largely unknown.
Purpose of the Study:
- To investigate the regulatory mechanisms of caspase-14 expression.
- To determine the role of sphingolipids, particularly ceramides, in regulating caspase-14 expression.
Main Methods:
- Cultured human keratinocytes were treated with various sphingolipids.
- Caspase-14 expression (mRNA and protein) was analyzed.
- Inhibitors of sphingolipid metabolism were used to assess regulatory roles.
Main Results:
- Specific ceramides (C(2)-Cer, C(6)-Cer) dose- and time-dependently increased caspase-14 expression.
- Inhibitors of glucosylceramide synthase and ceramidase also increased caspase-14 expression.
- Ceramide-induced increase in caspase-14 expression requires new protein synthesis and is primarily mediated by increased gene transcription.
Conclusions:
- Ceramides play a significant role in stimulating caspase-14 expression in keratinocytes.
- This provides a mechanism for coordinating lipid lamellar membrane formation with corneocyte formation.
- Basal caspase-14 expression is not dependent on de novo ceramide synthesis.
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