Epidermal permeability barrier function and sphingolipid content in the skin of sphingomyelin synthase 2 deficient mice

Abstract

Background

Sphingomyelin synthase (SMS) is an enzyme that generates sphingomyelin (SM) from ceramide (CER) and phosphatidylcholine. SM in the epidermis is a precursor of CER, an important lipid for epidermal permeability barrier function. However, the physiological role of SMS in skin is unclear.

Objectives

To uncover the function of SMS in skin, we investigated sphingolipid metabolism enzyme activity in skin, SM content in the epidermis, CER content in the stratum corneum (SC) and transepidermal water loss (TEWL) as an indicator of barrier function in SMS2-knockout (KO) mice.

Methods

The activities of sphingolipid metabolism enzymes in skin homogenates were measured using a fluorescently labeled substrate. Enzymatic reaction products were detected by high performance liquid chromatography (HPLC). Lipids in the epidermis or SC were extracted and quantified by high performance thin layer chromatography (HPTLC). TEWL was measured using a Tewameter TM300.

Results

In SMS2-KO mice, SMS activity in skin homogenates, epidermal SM content and SC CER content were significantly decreased relative to wild type (WT) mice. The TEWL of SMS2-KO mice was significantly increased compared to WT mice.

Conclusion

Our data indicate that SMS2 generate SM in the epidermis and contribute to epidermal permeability barrier function and will support understanding of SM related metabolic disorders.

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