Tissue-specific mRNA expression profiles of human nuclear receptor subfamilies.
Tissue-specific mRNA expression profiles of human nuclear receptor subfamilies.
复制标题
DOI：
10.2133/dmpk.19.135
复制
发表时间：
2004-04-01
影响因子：
2.1
通讯作者：
Yokoi, Tsuyoshi
中科院分区：
文献类型：
--
作者：
Nishimura, Masuhiro;Naito, Shinsaku;Yokoi, Tsuyoshi
制备对每种人核受体特异性的正向和反向引物对和TaqMan探针。分析来自各种人体器官的单个和混合样本的总RNA中43种核受体的每个靶点的mRNA表达水平（肝、肾、肾上腺、肺、心脏、脑、小脑、骨骼肌、脾、胸腺、甲状腺、前列腺、睾丸、子宫、胎盘、骨髓、气管，和唾液腺）通过使用ABI PRISM 7700序列检测系统的实时逆转录PCR进行。33种核受体的mRNA表达（NR1A1，1A2，1B1，1B2，1B3，1C1，1C2，1C3，1D1，1D2，1F1，1F2，1F3，1H2，1H3，1I1，1I2，2B1，2B2，2B3，2C1，2C2，2F1，2F2，3A2，3B1，3C1，3C2，3C4，4A1，4A2，4A3，和6A1）通过该方法在所有组织中成功地检测到。NR1H4、2A1和3C3 mRNA分别在心脏、心脏和肝脏中未检测到。NR5A2 mRNA在脑和小脑中均未检测到。NR3A1 mRNA在小肠、结肠、脑和小脑中未检测到。在肾脏、胃、小肠和结肠中未检测到NR5A1 mRNA。在肝脏、肾脏、胃、小肠、肾上腺、肺、脑、骨骼肌、胸腺、甲状腺、前列腺、睾丸、胎盘和气管中检测到NR1I3 mRNA。在肝脏、肾脏、前列腺、睾丸、子宫和气管中检测到NR2A2 mRNA。在肾上腺、脑、小脑、睾丸、胎盘和骨髓中检测到NR2E1 mRNA。NR2E3 mRNA在肾上腺、甲状腺、前列腺、睾丸、子宫、气管和唾液腺中均有表达。本研究提供了43种人核受体mRNA表达的组织分布信息。还显示了CYP 3A 4、CYP 3A 5和ABC转运蛋白的mRNA表达谱。这些结果对于建立一个核受体介导的新药筛选系统具有重要的参考价值。
Pairs of forward and reverse primers and TaqMan probes specific to each human nuclear receptor were prepared. Analysis of the mRNA expression level of each target of 43 nuclear receptors in total RNA from single and pooled specimens of various human organs (liver, kidney, adrenal gland, lung, heart, brain, cerebellum, skeletal muscle, spleen, thymus, thyroid gland, prostate, testis, uterus, placenta, bone marrow, trachea, and salivary gland) was performed by real-time reverse transcription PCR using an ABI PRISM 7700 sequence detector system. The mRNA expression of 33 nuclear receptors (NR1A1, 1A2, 1B1, 1B2, 1B3, 1C1, 1C2, 1C3, 1D1, 1D2, 1F1, 1F2, 1F3, 1H2, 1H3, 1I1, 1I2, 2B1, 2B2, 2B3, 2C1, 2C2, 2F1, 2F2, 3A2, 3B1, 3C1, 3C2, 3C4, 4A1, 4A2, 4A3, and 6A1) was successfully detected in all of the tissues by this method. NR1H4, 2A1, and 3C3 mRNAs were not detectable in the heart, heart, and liver, respectively. NR5A2 mRNA was not detectable in either the brain or cerebellum. NR3A1 mRNA was not detectable in the small intestine, colon, brain, and cerebellum. NR5A1 mRNA was not detectable in the kidney, stomach, small intestine, and colon. NR1I3 mRNA was detected in the liver, kidney, stomach, small intestine, adrenal gland, lung, brain, skeletal muscle, thymus, thyroid gland, prostate, testis, placenta, and trachea. NR2A2 mRNA was detected in the liver, kidney, prostate, testis, uterus, and trachea. NR2E1 mRNA was detected in the adrenal gland, brain, cerebellum, testis, placenta, and bone marrow. NR2E3 mRNA was detected in the adrenal gland, thyroid gland, prostate, testis, uterus, trachea, and salivary gland. This study provides information concerning the tissue distribution of the mRNA expression of 43 human nuclear receptors. The mRNA expression profiles of CYP3A4, CYP3A5 and ABC-transporters are also shown. These results are valuable for establishing a nuclear receptor-mediated screening system for new chemical entities in new drug development.