Kim Hye-Ryoung, Park Sung-Won, Cho Hee-Jung, Chae Kyung-Ae, Sung Ji-Min, Kim Jin-Suk, Landowski Christopher P, Sun Duxin, Abd El-Aty A M, Amidon Gordon L, Shin Ho-Chul
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
Pharmacol Res. 2007 Sep;56(3):224-36. doi: 10.1016/j.phrs.2007.06.005. Epub 2007 Jun 23.
We have studied gene expression profiles of intestinal transporters in model animals and humans. Total RNA was isolated from duodenum and the mRNA expression was measured using Affymetrix GeneChip oligonucleotide arrays. Detected genes from the intestine of mice, rats, and humans were about 60% of 22,690 sequences, 40% of 8739, and 47% of 12,559, respectively. A total of 86 genes involving transporters expressed in mice, 50 genes in rats, and 61 genes in humans were detected. Mice exhibited abundant mRNA expressions for peptide transporter HPT1, amino acid transporters CSNU3, CT1 and ASC1, nucleoside transporter CNT2, organic cation transporter SFXN1, organic anion transporter NBC3, glucose transporter SGLT1, and fatty acid transporters FABP1 and FABP2. Rats showed high expression profiles of peptide transporter PEPT1, amino acid transporters CSNU1 and 4F2HC, nucleoside transporter CNT2, organic cation transporter OCT5, organic anion transporter SDCT1, glucose transporter GLUT2 and GLUT5, and folate carrier FOLT. In humans, the highly expressed genes were peptide transporter HPT1, amino acid transporters LAT3, 4F2HC and PROT, nucleoside transporter CNT2, organic cation transporter OCTN2, organic anion transporters NADC1, NBC1 and SBC2, glucose transporters SGLT1 and GLUT5, multidrug resistance-associated protein RHO12, fatty acid transporters FABP1 and FABP2, and phosphate carrier PHC. Overall these data reveal diverse transcriptomic profiles for intestinal transporters among these species. Therefore, this transcriptional data may lead to more effective use of the laboratory animals as a model for oral drug development.
我们研究了模式动物和人类肠道转运体的基因表达谱。从十二指肠分离总RNA,并使用Affymetrix GeneChip寡核苷酸阵列测量mRNA表达。从小鼠、大鼠和人类肠道中检测到的基因分别约占22,690个序列的60%、8739个序列的40%和12,559个序列的47%。共检测到86个在小鼠中表达的涉及转运体的基因、50个在大鼠中表达的基因和61个在人类中表达的基因。小鼠在肽转运体HPT1、氨基酸转运体CSNU3、CT1和ASC1、核苷转运体CNT2、有机阳离子转运体SFXN1、有机阴离子转运体NBC3、葡萄糖转运体SGLT1以及脂肪酸转运体FABP1和FABP2方面表现出丰富的mRNA表达。大鼠在肽转运体PEPT1、氨基酸转运体CSNU1和4F2HC、核苷转运体CNT2、有机阳离子转运体OCT5、有机阴离子转运体SDCT1、葡萄糖转运体GLUT2和GLUT5以及叶酸载体FOLT方面表现出高表达谱。在人类中,高表达基因包括肽转运体HPT1、氨基酸转运体LAT3、4F2HC和PROT、核苷转运体CNT2、有机阳离子转运体OCTN2、有机阴离子转运体NADC1、NBC1和SBC2、葡萄糖转运体SGLT1和GLUT5、多药耐药相关蛋白RHO12、脂肪酸转运体FABP1和FABP2以及磷酸盐载体PHC。总体而言,这些数据揭示了这些物种之间肠道转运体不同的转录组谱。因此,这种转录数据可能会使实验动物在口服药物开发模型中得到更有效的利用。