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
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Diseases presenting "cultured human keratinocyte" symptom

harlequin ichthyosis

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