Metabolism Section, Veterans Affairs Medical Center, Northern California Institute for Research and Education, University of California at San Francisco, San Francisco, CA 94121, USA.
J Lipid Res. 2010 Nov;51(11):3185-95. doi: 10.1194/jlr.M006445. Epub 2010 Aug 1.
ABCG1, a member of the ATP binding cassette superfamily, facilitates the efflux of cholesterol from cells to HDL. In this study, we demonstrate that ABCG1 is expressed in cultured human keratinocytes and murine epidermis, and induced during keratinocyte differentiation, with increased levels in the outer epidermis. ABCG1 is regulated by liver X receptor (LXR) and peroxisome proliferator-activated receptor-δ (PPAR-δ) activators, cellular sterol levels, and acute barrier disruption. Both LXR and PPAR-δ activators markedly stimulate ABCG1 expression in a dose- and time-dependent fashion. PPAR-γ activators also increase ABCG1 expression, but to a lesser degree. In contrast, activators of PPAR-α, retinoic acid receptor, retinoid X receptor, and vitamin D receptor do not alter ABCG1 expression. In response to increased intracellular sterol levels, ABCG1 expression increases, whereas inhibition of cholesterol biosynthesis decreases ABCG1 expression. In vivo, ABCG1 is stimulated 3-6 h after acute barrier disruption by either tape stripping or acetone treatment, an increase that can be inhibited by occlusion, suggesting a potential role of ABCG1 in permeability barrier homeostasis. Although Abcg1-null mice display normal epidermal permeability barrier function and gross morphology, abnormal lamellar body (LB) contents and secretion leading to impaired lamellar bilayer formation could be demonstrated by electron microscopy, indicating a potential role of ABCG1 in normal LB formation and secretion.
ABCG1 是 ATP 结合盒超家族的成员之一，有助于胆固醇从细胞中流出到 HDL。在本研究中，我们证明 ABCG1 在培养的人角质形成细胞和鼠表皮中表达，并在角质形成细胞分化过程中诱导表达，在外表皮中表达水平增加。ABCG1 受肝 X 受体 (LXR) 和过氧化物酶体增殖物激活受体-δ (PPAR-δ) 激活剂、细胞固醇水平和急性屏障破坏的调节。LXR 和 PPAR-δ 激活剂均以剂量和时间依赖的方式显著刺激 ABCG1 的表达。PPAR-γ 激活剂也增加 ABCG1 的表达，但程度较小。相比之下，PPAR-α、维甲酸受体、视黄酸受体和维生素 D 受体的激活剂不会改变 ABCG1 的表达。细胞内固醇水平增加时，ABCG1 的表达增加，而胆固醇生物合成的抑制则降低 ABCG1 的表达。在体内，通过胶带剥离或丙酮处理急性破坏屏障后 3-6 小时，ABCG1 表达增加，而胆固醇生物合成的抑制可减少 ABCG1 的表达。ABCG1 敲除小鼠显示正常的表皮渗透屏障功能和大体形态，但电镜显示板层小体 (LB) 含量和分泌异常，导致板层双层形成受损，表明 ABCG1 在正常 LB 形成和分泌中可能发挥作用。
