title: The effect of hepatocyte growth factor on gene transcription during intestinal adaptation.
abstract: OBJECTIVE
  Previously, we investigated the physiologic effects of hepatocyte growth factor (HGF) on intestinal adaptation using a massive small bowel resection (MSBR) rat model. To correlate these altered physiologic changes with gene alterations, we used microarray technology at 7, 14, and 21 days after MSBR.
  
  
  METHODS
  Forty-five adult female rats were divided into 3 groups and underwent 70% MSBR, MSBR + HGF (intravenous 150 μg/kg per day), or sham operation (control). Five animals per group were killed at each time point. Ileal mucosa was harvested and RNA extracted. Rat Gene Chips and Expression Console software (Affymetrix, Santa Clara, CA) were used. Statistical analysis was done by analysis of variance using Partek Genomics Suite (Partek, Inc, St Louis, MO). Results were significant if fold change was more than 2 or less than -2, with P < .05.
  
  
  RESULTS
  Compared with the control group, MSBR group had significant increases in up-regulated and down-regulated genes. The MSBR-HGF group had further increases in up-regulated and down-regulated genes compared with the MSBR group. At 7 days, 6 cellular hypertrophy families had 30 genes up-regulated, and HGF up-regulated an additional 14 genes. At 21 days, 5 hyperplasia gene families had 32 up-regulated genes. Hepatocyte growth factor up-regulated an additional 16 genes.
  
  
  CONCLUSIONS
  Microarray analysis of intestinal adaptation identified an early emphasis on hypertrophy and later emphasis on hyperplasia. This is the first demonstration that the effect of HGF on intestinal adaptation is recruitment of more genes rather than an increase in the fold change of already up-regulated genes.
authors.affiliation: Department of Surgery, St Christopher's Hospital for Children, Philadelphia, PA 19134, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Katz
authors.forename: Keith A
authors.initials: KA
authors.lastname: Thatch
authors.forename: Marshall Z
authors.initials: MZ
authors.lastname: Schwartz
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation; D020895:Enterocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D007082:Ileum / Q000187:drug effects / Q000601:surgery; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects / Q000502:physiology / Q000601:surgery*; D005810:Multigene Family / Q000187:drug effects* / Q000235:genetics*; D040081:Protein Array Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012778:Short Bowel Syndrome; D014158:Transcription, Genetic / Q000187:drug effects* / Q000502:physiology; D015854:Up-Regulation
chemical_list: D017228:Hepatocyte Growth Factor