Higashiyama Hiroyuki, Kinoshita Mine, Asano Satoshi
Tsukuba Research Laboratories, Pharmacology Department, GlaxoSmithKline, 43 Wadai, Tsukuba, Ibaraki 300-4247, Japan.
Acta Histochem. 2008;110(1):86-93. doi: 10.1016/j.acthis.2007.08.001. Epub 2007 Oct 25.
Farnesoid X receptor (FXR) is a member of the nuclear receptor family and is known to play important roles in bile acid homeostasis, and lipid and glucose metabolism. In this study, to elucidate the systemic physiological functions of FXR, comprehensive immunohistochemical analysis of cell/subcellular localization of FXR and its heterodimer partner, retinoid X receptor (RXR)-alpha, in adult mice tissues was performed using tissue microarray (TMA)-based immunohistochemistry. FXR immunolabeling was observed in the enterohepatic system--including absorptive epithelium in the intestines, hepatocytes and gall bladder epithelium, several epithelial lineage cells including the basal cells of stratified epithelium in the tongue, esophagus, forestomach--skin, corneal epithelium and ciliary body epithelium in the eye and adrenocortical cells--including glandular cells in the zona reticularis/fasciculata. In these FXP-positive cells, FXR was preferentially localized to the nucleus. RXR-alpha was ubiquitously distributed in the nucleus of most cell types, including FXR-positive cell types in the examined tissues. These data suggest that FXR might have various physiological roles, not only in bile acid homeostasis, and lipid and glucose metabolism, but also in the epithelial cell barrier, visual and urinary function through multiple organ systems.
法尼酯X受体(FXR)是核受体家族的成员之一,已知其在胆汁酸稳态以及脂质和葡萄糖代谢中发挥重要作用。在本研究中,为阐明FXR的全身生理功能,利用基于组织微阵列(TMA)的免疫组织化学方法,对成年小鼠组织中FXR及其异源二聚体伴侣维甲酸X受体(RXR)-α的细胞/亚细胞定位进行了全面的免疫组织化学分析。在肠肝系统中观察到FXR免疫标记,包括肠道中的吸收上皮、肝细胞和胆囊上皮,几种上皮谱系细胞,包括舌、食管、前胃的复层上皮基底细胞、皮肤、眼的角膜上皮和睫状体上皮以及肾上腺皮质细胞,包括网状带/束状带中的腺细胞。在这些FXR阳性细胞中,FXR优先定位于细胞核。RXR-α广泛分布于大多数细胞类型的细胞核中,包括所检测组织中的FXR阳性细胞类型。这些数据表明,FXR可能不仅在胆汁酸稳态以及脂质和葡萄糖代谢中,而且在通过多个器官系统的上皮细胞屏障、视觉和泌尿功能中具有多种生理作用。