Dynamic regulation of retinoic acid-binding proteins in developing, adult and neoplastic skin reveals roles for β-catenin and Notch signalling
Dynamic regulation of retinoic acid-binding proteins in developing, adult and neoplastic skin reveals roles for β-catenin and Notch signalling
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DOI：
10.1016/j.ydbio.2008.08.034
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发表时间：
2008-12-01
影响因子：
2.7
通讯作者：
Watt, Fiona M.
中科院分区：
文献类型：
--
作者：
Collins, Charlotte A.;Watt, Fiona M.
视黄酸（RA）信号是表皮分化所必需的，然而，它的作用机制在很大程度上是未知的。RA在不同核受体之间的分配受RA结合蛋白的调节。我们发现，细胞RA结合蛋白CRAB 1和CRABP 2和脂肪酸结合蛋白FABP 5在皮肤发育和成人组织中动态表达。CRAB 1在胚胎真皮和皮肤肿瘤的基质中表达，但仅限于正常出生后皮肤的毛囊毛乳头。CRABP 2和FABP 5在皮脂腺、毛囊间表皮和毛囊的分化细胞中表达，其中FABP 5是皮脂腺和生长期毛囊球的重要标志物。所有三种蛋白质响应于RA处理或Notch活化而上调，并且通过Wnt/β-连环蛋白信号传导负调节。由β-连环蛋白诱导的异位毛囊产生于已经失去CRABP 2和FABP 5的皮脂腺区域：相反，通过N-末端截短的Lef 1抑制毛囊形成导致CRABP 2和FABP 5的上调。我们的研究结果表明，在皮肤的不同区域有RA信号的动态调节，并为RA，β-连环蛋白和Notch通路之间的相互作用提供了证据。(C)2008年，爱思唯尔。All rights reserved.
Retinoic acid (RA) signalling is essential for epidermal differentiation; however, the mechanisms by which it acts are largely unexplored. Partitioning of RA between different nuclear receptors is regulated by RA-binding proteins. We show that cellular RA-binding proteins CRAB1 and CRABP2 and the fatty acid-binding protein FABP5 are dynamically expressed during skin development and in adult tissue. CRAB1 is expressed in embryonic dermis and in the stroma of skin tumours, but confined to the hair follicle dermal papilla in normal postnatal skin. CRABP2 and FABP5 are expressed in the differentiating cells of sebaceous gland, interfollicular epidermis and hair follicles, with FABP5 being a prominent marker of sebaceous glands and anagen follicle bulbs. All three proteins are upregulated in response to RA treatment or Notch activation and are negatively regulated by Wnt/beta-catenin signalling. Ectopic follicles induced by beta-catenin arise from areas of the sebaceous gland that have lost CRABP2 and FABP5: conversely, inhibition of hair follicle formation by N-terminally truncated Lef1 results in upregulation of CRABP2 and FABP5. Our findings demonstrate that there is dynamic regulation of RA signalling in different regions of the skin and provide evidence for interactions between the RA, beta-catenin and Notch pathways. (C) 2008 Elsevier in. All rights reserved.