PPAR and LXR activators regulate ABCA12 expression in human keratinocytes.

[harlequin ichthyosis]

ATP-binding cassette (ABC ) transporter , family 12 (ABCA 12 ), a member of the ABC superfamily , facilitates the delivery of lipids to lamellar bodies (LB ) in keratinocytes , which is critical for permeability barrier function . Recently , gene mutations of ABCA 12 were found to underlie Harlequin ichthyosis and lamellar ichthyosis , two devastating skin disorders . Previously we and others have demonstrated that peroxisome proliferators-activated receptors (PPARs ) and liver X receptor (LXR ) activation improved epidermal permeability barrier homeostasis by stimulating keratinocyte differentiation , lipid synthesis , and increasing LB formation /secretion . Here we report that both PPAR-gamma and -beta /delta activators markedly stimulate ABCA 12 mRNA expression in cultured human keratinocyte (CHK ) in a dose- and time-dependent manner . Increased ABCA 12 mRNA levels are accompanied by an increase in ABCA 12 protein , suggesting biological importance of this upregulation . LXR activators also increase ABCA 12 mRNA levels in CHK , but to a lesser extent . In contrast , activators of PPAR-alpha , RAR , RXR , or vitamin D receptor did not alter ABCA 12 expression . Two major ABCA 12 alternative transcripts and their corresponding proteins are also expressed and upregulated by PPAR or LXR activator in both undifferentiated and differentiated CHK . Together , our data demonstrate that PPAR and LXR activators increase ABCA 12 expression , providing an additional mechanism by which PPAR and LXR activators promote epidermal permeability barrier homeostasis .

Diseases
Validation

Diseases presenting "ichthyosis" symptom

child syndrome

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

harlequin ichthyosis

hirschsprung disease

junctional epidermolysis bullosa

kallmann syndrome

lamellar ichthyosis

This symptom has already been validated