GPR39 splice variants versus antisense gene LYPD1:: Expression and regulation in gastrointestinal tract, endocrine pancreas, liver, and white adipose tissue
GPR39 splice variants versus antisense gene LYPD1:: Expression and regulation in gastrointestinal tract, endocrine pancreas, liver, and white adipose tissue
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DOI：
10.1210/me.2007-0055
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发表时间：
2007-07-01
影响因子：
--
通讯作者：
Schwartz, Thue W.
中科院分区：
文献类型：
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作者：
Egerod, Kristoffer L.;Holst, Birgitte;Schwartz, Thue W.
G蛋白偶联受体39（GPR39）是胃饥饿素受体家族中一种组成性激活的孤儿成员，可被锌离子激活。在此描述GPR39以一种具有生物活性的全长七跨膜形式GPR39 - 1a，以及一种截短的剪接变体五跨膜形式GPR39 - 1b表达。GPR39基因的3'外显子与一个称为LYPD1（含Ly - 6/PLAUR结构域1）的反义基因重叠。定量逆转录聚合酶链反应分析表明，GPR39 - 1a在整个胃肠道（包括肝脏和胰腺）以及肾脏和脂肪组织中选择性表达，而截短的GPR39 - 1b形式具有更广泛的表达模式，包括中枢神经系统，但在胃和小肠中表达最高。相比之下，LYPD1反义基因在整个中枢神经系统中高度表达，这通过定量逆转录聚合酶链反应和原位杂交分析得以确定。对GPR39启动子区域的功能分析确定了肝细胞核因子1α和4α（HNF - 1α和 - 4α）以及特异性蛋白1（SP1）转录因子的位点对GPR39的表达很重要。在大鼠体内实验表明，在禁食期间以及对链脲佐菌素处理有反应时，脂肪组织中的GPR39会上调，尽管在同一动物的肝脏中其表达保持恒定。GPR39 - 1a在白色脂肪组织中表达，但不在棕色脂肪组织中表达，并且在成纤维细胞的脂肪细胞分化过程中下调。结论是，转录控制机制、组织表达模式以及对生理刺激的体内反应都表明GPR39受体很可能对包括肝脏、胃肠道、胰腺和脂肪组织在内的许多代谢器官的功能具有重要意义。
G protein-coupled receptor 39 (GPR39) is a constitutively active, orphan member of the ghrelin receptor family that is activated by zinc ions. GPR39 is here described to be expressed in a full-length, biologically active seven-transmembrane form, GPR39-1a, as well as in a truncated splice variant five-transmembrane form, GPR39-1b. The 3' exon of the GPR39 gene overlaps with an antisense gene called LYPD1 (Ly-6/PLAUR domain containing 1). Quantitative RT-PCR analysis demonstrated that GPR39-1a is expressed selectively throughout the gastrointestinal tract, including the liver and pancreas as well as in the kidney and adipose tissue, whereas the truncated GPR39-1b form has a more broad expression pattern, including the central nervous system but with highest expression in the stomach and small intestine. In contrast, the LYPD1 antisense gene is highly expressed throughout the central nervous system as characterized with both quantitative RT-PCR and in situ hybridization analysis. A functional analysis of the GPR39 promoter region identified sites for the hepatocyte nuclear factors 1 alpha and 4 alpha (HNF-1 alpha and -4 alpha) and specificity protein 1 (SP1) transcription factors as being important for the expression of GPR39. In vivo experiments in rats demonstrated that GPR39 is up-regulated in adipose tissue during fasting and in response to streptozotocin treatment, although its expression is kept constant in the liver from the same animals. GPR39-1a was expressed in white but not brown adipose tissue and was down-regulated during adipocyte differentiation of fibroblasts. It is concluded that the transcriptional control mechanism, the tissue expression pattern, and in vivo response to physiological stimuli all indicate that the GPR39 receptor very likely is of importance for the function of a number of metabolic organs, including the liver, gastrointestinal tract, pancreas, and adipose tissue.