title: Changes in the transcriptional profile of transporters in the intestine along the anterior-posterior and crypt-villus axes.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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 < or = 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 < or = 0.05) along the anterior-posterior axis was observed.
  
  
  CONCLUSIONS
  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.
authors.affiliation: ISREC, Swiss Institute for Experimental Cancer Research, 1066 Epalinges s/Lausanne, Switzerland. pascale.anderle@isrec.ch
authors.forename: Pascale
authors.initials: P
authors.lastname: Anderle
authors.forename: Thierry
authors.initials: T
authors.lastname: Sengstag
authors.forename: David M
authors.initials: DM
authors.lastname: Mutch
authors.forename: Martin
authors.initials: M
authors.lastname: Rumbo
authors.forename: Viviane
authors.initials: V
authors.lastname: Praz
authors.forename: Robert
authors.initials: R
authors.lastname: Mansourian
authors.forename: Mauro
authors.initials: M
authors.lastname: Delorenzi
authors.forename: Gary
authors.initials: G
authors.lastname: Williamson
authors.forename: Matthew-Alan
authors.initials: MA
authors.lastname: Roberts
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001692:Biological Transport; D003106:Colon / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D007082:Ileum / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology*; D007834:Lasers; D008297:Male; D051379:Mice; D042282:Microdissection; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger