Changes in the transcriptional profile of transporters in the intestine along the anterior-posterior and crypt-villus axes.
Changes in the transcriptional profile of transporters in the intestine along the anterior-posterior and crypt-villus axes.
复制标题
DOI：
10.1186/1471-2164-6-69
复制
发表时间：
2005-05-10
期刊：
影响因子：
4.4
通讯作者：
Roberts, MA
中科院分区：
文献类型：
--
作者：
Anderle, P;Sengstag, T;Mutch, DM;Rumbo, M;Praz, V;Mansourian, R;Delorenzi, M;Williamson, G;Roberts, MA
这项工作的目的是表征药物和营养载体沿着肠上皮的前后轴和隐绒毛轴的表达，并研究利用整个肠道组织而不是纯化的上皮细胞来检测基因表达的区域差异的有效性。我们已经描述了沿肠道前后轴的所有已知转运体中76%的mRNA表达谱。这是第一个描述肠中大多数已知转运蛋白表达谱的研究。采用高密度微阵列技术检测小鼠十二指肠、空肠、回肠和结肠全组织中根据Gene Ontology consortium定义的转运蛋白的表达谱。对于9种转运蛋白（Abca1、Abcc1、Abcc3、abc8、Slc10a2、Slc28a2、Slc2a1、Slc34a2和Slc5a8），在上述肠道区域对应的激光微解剖隐窝和绒毛上皮细胞中进一步采用RT-PCR检测mRNA谱。对于差异调节的转运蛋白，结肠具有与小肠不同的表达谱。大多数（59% p截止值≤0.05）的转运蛋白mRNA水平在所研究的肠段中是恒定的。对于转运蛋白亚类“载体活性”，它包含大多数已知的生物活性化合物的载体，沿前后轴观察到显著变化（p≤0.05）。在激光解剖材料中检查的所有九种转运蛋白都表现出与微阵列显示的区域特异性谱的良好复制。此外，我们认为Slc5a8沿着肠道的分布特征使其成为肠道后部单羧酸类药物的合适候选载体。我们的研究结果还预测，不同肠段对载体介导化合物的吸收有显著差异。最显著的差异可以预期在邻近的回肠和结肠段之间，但其他邻近段之间的差异是不可忽略的。最后，对于检测的基因，在全肠组织提取物中测量的谱代表了仅上皮细胞的基因表达。
The purpose of this work was to characterize the expression of drug and nutrient carriers along the anterior-posterior and crypt-villus axes of the intestinal epithelium and to study the validity of utilizing whole gut tissue rather than purified epithelial cells to examine regional variations in gene expression. We have characterized the mRNA expression profiles of 76 % of all currently known transporters along the anterior-posterior axis of the gut. This is the first study to describe the expression profiles of the majority of all known transporters in the intestine. The expression profiles of transporters, as defined according to the Gene Ontology consortium, were measured in whole tissue of the murine duodenum, jejunum, ileum and colon using high-density microarrays. For nine transporters (Abca1, Abcc1, Abcc3, Abcg8, Slc10a2, Slc28a2, Slc2a1, Slc34a2 and Slc5a8), the mRNA profiles were further measured by RT-PCR in laser micro-dissected crypt and villus epithelial cells corresponding to the aforementioned intestinal regions. With respect to differentially regulated transporters, the colon had a distinct expression profile from small intestinal segments. The majority (59 % for p cutoff ≤ 0.05) of transporter mRNA levels were constant across the intestinal sections studied. For the transporter subclass "carrier activity", which contains the majority of known carriers for biologically active compounds, a significant change (p ≤ 0.05) along the anterior-posterior axis was observed. All nine transporters examined in laser-dissected material demonstrated good replication of the region-specific profiles revealed by microarray. Furthermore, we suggest that the distribution characteristics of Slc5a8 along the intestinal tract render it a suitable candidate carrier for monocarboxylate drugs in the posterior portion of the intestine. Our findings also predict that there is a significant difference in the absorption of carrier-mediated compounds in the different intestinal segments. The most pronounced differences can be expected between the adjoining segments ileum and colon, but the differences between the other adjoining segments are not negligible. Finally, for the examined genes, profiles measured in whole intestinal tissue extracts are representative of epithelial cell-only gene expression.
登录
查看更多内容
影响因子：
14.9
作者：
Draghici, S;Khatri, P;Tainsky, MA
通讯作者：
Tainsky, MA
影响因子：
4.8
作者：
Dawson, PA;Haywood, J;Parks, JS
通讯作者：
Parks, JS
影响因子：
3.7
作者：
Anderle, P;Rakhmanova, V;Sadée, W
通讯作者：
Sadée, W
影响因子：
5.5
作者：
Chen, Z;Fei, YJ;Ganapathy, V
通讯作者：
Ganapathy, V
DOI：
10.1152/ajpgi.1998.274.1.g157
发表时间：
1998-01-01
影响因子：
4.5
作者：
Craddock, AL;Love, MW;Dawson, PA
通讯作者：
Dawson, PA