title: The correlation between the expression of differentiation markers in rat small intestinal mucosa and the transcript levels of schlafen 3.
abstract: OBJECTIVE
  The normal absorptive function and structural maintenance of the intestinal mucosa depend on a constant process of proliferation of enterocytic stem cells followed by progressive differentiation toward a mature phenotype. The mechanisms that govern enterocytic differentiation in the mucosa of the small intestine are poorly understood.
  
  
  OBJECTIVE
  To determine whether schlafen 3 (but not other schlafen proteins) act in vivo and whether its effects are limited to the small intestine. We have previously demonstrated in nonmalignant rat intestinal IEC-6 cells that schlafen 3 levels correlate with the expression of various differentiation markers in vitro in response to differentiation stimuli.
  
  
  METHODS
  Randomized controlled experiment.
  
  
  METHODS
  Animal science laboratory.
  
  
  METHODS
  Male Sprague-Dawley rats 8 to 13 weeks old.
  
  
  METHODS
  Messenger RNA (mRNA) from jejunal and colonic mucosa was isolated, and transcript levels of schlafen proteins 1, 2, 3, 4, 5, 13, and 14; sucrase isomaltase (SI); dipeptidyl peptidase 4 (Dpp4); glucose transporter type 2 (Glut2); and villin were measured by quantitative reverse transcriptase-polymerase chain reaction. We tested parallel variations in protein levels by Western blotting and Dpp4 enzyme activity.
  
  
  RESULTS
  The transcript level of schlafen 3 (Slfn3) correlated with the levels of the differentiation markers SI, Dpp4, Glut2, and villin. However, the expression of schlafen proteins 1, 2, 4, 5, 13, and 14 did not correlate with the expression of the differentiation markers. The mucosal mRNA levels of Slfn3, SI, Glut2, and Dpp4 were all substantially higher in the rat jejunum than in colonic mucosa by a mean (SE) factor of 51.0 (13.2) for 6 rats (P < .05), 599 (99) for 8 rats (P < .01), 12.5 (5.5) for 8 rats (P < .01), and 14.0 (3.9) for 8 rats (P < .01), respectively. In IEC-6 cells, infection with adenovirus-expressing GFP-tagged Slfn3 significantly increased Slfn3 expression and Dpp4-specific activity compared with GFP-expressing virus (in 6 rats; P < .05).
  
  
  CONCLUSIONS
  Taken together with our previous in vitro observations, the results suggest that small intestinal enterocytic epithelial differentiation in rats may be regulated by Slfn3 in vivo, as in vitro, and that these effects may be specific to the small intestinal enterocytic phenotype as opposed to that of the mature colonocyte. Slfn3 human orthologs may be targeted to stimulate intestinal differentiation in patients with short bowel syndrome.
authors.affiliation: Department of Surgery, Michigan State University, East Lansing.
authors.forename: Pavlo L
authors.initials: PL
authors.lastname: Kovalenko
authors.forename: Marc D
authors.initials: MD
authors.lastname: Basson
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D003106:Colon / Q000166:cytology / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism; D007082:Ileum / Q000166:cytology / Q000378:metabolism*; D007583:Jejunum / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013394:Sucrase-Isomaltase Complex / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051273:Glucose Transporter Type 2; D008840:Microfilament Proteins; D011506:Proteins; D012333:RNA, Messenger; C541111:Slfn4 protein, rat; C026615:villin; D013394:Sucrase-Isomaltase Complex; D018819:Dipeptidyl Peptidase 4