Immunolocalization of enzymes, binding proteins, and receptors sufficient for retinoic acid synthesis and signaling during the hair cycle
Immunolocalization of enzymes, binding proteins, and receptors sufficient for retinoic acid synthesis and signaling during the hair cycle
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DOI：
10.1038/sj.jid.5700753
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发表时间：
2007-07-01
影响因子：
6.5
通讯作者：
Ong, David E.
中科院分区：
文献类型：
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作者：
Everts, Helen B.;Sundberg, John P.;Ong, David E.
维甲酸（RA）是维持大多数上皮组织所必需的。一种RA生物合成途径由细胞视黄醇结合蛋白（Crbp）、视黄醇脱氢酶（Dhrs 9/eRoldh）、视黄醇脱氢酶1-3（Aldh 1a 1 -3）和细胞RA结合蛋白2（Crabp 2）组成。在此之前，我们将Aldh 1a 2和Aldh 1a 3定位于整个毛发周期中毛囊内的上皮细胞和间充质细胞。本研究通过在C57 BL/6 J小鼠中检查RA生物合成的完整途径以及通过RA受体α、β和γ的信号传导来扩展观察结果，所述C57 BL/6 J小鼠蜡剥离以启动和同步周期。RA生物合成和信号传导的这一途径以毛发周期依赖的方式定位于毛囊、皮脂腺和毛囊间表皮的大多数层，表明毛囊内的RA生物合成以空间和时间的方式进行调节。这种定位模式还揭示了RA生物合成和信号通路内上皮-间充质相互作用和分化状态差异的见解，以及Crabp 2和RA受体的核与细胞质定位的新观察结果。这种复杂的RA生物合成和信号转导的免疫定位表明，内源性RA调节毛囊生长，分化和周期的特定方面。
Retinoic acid (RA) is essential for maintenance of most epithelial tissues. One RA biosynthesis pathway consists of cellular retinol-binding protein (Crbp), retinol dehydrogenase (Dhrs9/eRoldh), retinal dehydrogenase 1-3 (Aldh1a1-3), and cellular RA-binding protein 2 (Crabp2). Previously, we localized Aldh1a2 and Aldh1a3 to both epithelial and mesenchymal cells within the hair follicle throughout the hair cycle. This study expands that observation by examining the complete pathway of RA biosynthesis and signaling via RA receptors alpha, beta, and gamma by immunohistochernistry in C57BL/6J mice wax-stripped to initiate and synchronize the cycle. This pathway of RA biosynthesis and signaling localized to the majority of layers of the hair follicle, sebaceous gland, and interfollicular epidermis in a hair cycle-dependent manner, suggesting that RA biosynthesis within the hair follicle is regulated in both a spatial and temporal manner. This localization pattern also revealed insights into epithelial-mesenchymal interactions and differentiation state differences within the RA biosynthesis and signaling pathway, as well as novel observations on nuclear versus cytoplasmic localization of Crabp2 and RA receptors. This complex pattern of RA biosynthesis and signaling identified by immunolocalization suggests that endogenous RA regulates specific aspects of hair follicle growth, differentiation, and cycling.