title: Regulation of retinoblastoma protein (Rb) by p21 is critical for adaptation to massive small bowel resection.
abstract: BACKGROUND
  Adaptation following massive intestinal loss is characterized by increased villus height and crypt depth. Previously, we demonstrated that p21-null mice do not adapt after small bowel resection (SBR). As retinoblastoma protein (Rb) levels are elevated in p21-null crypt cells, we first sought to determine whether Rb is required for normal adaptation. Next, we tested whether Rb expression is responsible for blocked adaptation in p21-nulls.
  
  
  METHODS
  Genetically manipulated mice and wild-type (WT) littermates underwent either 50% SBR or sham operation. The intestine was harvested at 3, 7, or 28 days later and intestinal adaptation was evaluated. Enterocytes were isolated and protein levels evaluated by Western blot and quantified by optical density.
  
  
  RESULTS
  Rb-null mice demonstrated increased villus height, crypt depth, and proliferative rate at baseline, but there was no further increase following SBR. Deletion of one Rb allele lowered Rb expression and restored resection-induced adaptation responses in p21-null mice.
  
  
  CONCLUSIONS
  Rb is specifically required for resection-induced adaptation. Restoration of adaptation in p21-null mice by lowering Rb expression suggests a crucial mechanistic role for Rb in the regulation of intestinal adaptation by p21.
authors: Division of Pediatric Surgery, St. Louis Children's Hospital, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
authors: Jennifer A
authors: JA
authors: Leinicke
authors: Shannon
authors: S
authors: Longshore
authors: Derek
authors: D
authors: Wakeman
authors: Jun
authors: J
authors: Guo
authors: Brad W
authors: BW
authors: Warner
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007421:Intestine, Small / Q000473:pathology / Q000502:physiology* / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016160:Retinoblastoma Protein