12R-lipoxygenase deficiency disrupts epidermal barrier function

被引:153
作者
Epp, Nikolas
Fuerstenberger, Gerhard
Mueller, Karsten
de Juanes, Silvia
Leitges, Michael
Hausser, Ingrid
Thieme, Florian
Liebisch, Gerhard
Schmitz, Gerd
Krieg, Peter [1 ]
机构
[1] German Canc Res Ctr, Sect Eicosanoids & Tumor Dev, D-69120 Heidelberg, Germany
[2] Univ Oslo, Ctr Biotechnol, N-0317 Oslo, Norway
[3] Univ Clin Heidelberg, Dept Dermatol, D-69115 Heidelberg, Germany
[4] Univ Regensburg, Inst Clin Chem, D-93042 Regensburg, Germany
关键词
-;
D O I
10.1083/jcb.200612116
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
12R-lipoxygenase (12R-LOX) and the epidermal LOX-3 (eLOX-3) constitute a novel LOX pathway involved in terminal differentiation in skin. This view is supported by recent studies showing that inactivating mutations in 12R-LOX and eLOX-3 are linked to the development of autosomal recessive congenital ichthyosis. We show that 12R-LOX deficiency in mice results in a severe impairment of skin barrier function. Loss of barrier function occurs without alterations in proliferation and stratified organization of the keratinocytes, but is associated with ultrastructural anomalies in the upper granular layer, suggesting perturbance of the assembly/extrusion of lamellar bodies. Cornified envelopes from skin of 12R-LOX-deficient mice show increased fragility. Lipid analysis demonstrates a disordered composition of ceramides, in particular a decrease of ester-bound ceramide species. Moreover, processing of profilaggrin to monomeric filaggrin is impaired. This study indicates that the 12R-LOX-eLOX-3 pathway plays a key role in the process of epidermal barrier acquisition by affecting lipid metabolism, as well as protein processing.
引用
收藏
页码:173 / 182
页数:10
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