title: Bax is required for resection-induced changes in apoptosis, proliferation, and members of the extrinsic cell death pathways.
abstract: OBJECTIVE
  To define better the homeostatic mechanisms contributing to small intestinal adaptation following partial resection, the relative contributions of apoptosis, cell proliferation, and enterocyte migration and the comparative roles of the intrinsic (mitochondrial) and extrinsic (death receptor-mediated) apoptotic pathways were assessed.
  
  
  METHODS
  After 50% jejunoileal resections or transections, adaptation was analyzed in duodenal-jejunal and ileal segments from C57BL/6 Bax(+/+) (16, 48, and 168 hours postoperative) and Bax(-/-) mice (168 hours).
  
  
  RESULTS
  Basal apoptotic rates were equivalent in all mice. By 1-week postresection, villus heights and crypt depths were increased in the duodenal-jejunal and ileal remnants of both genotypes. In Bax(+/+) mice, adaptation occurred in concert with increased crypt proliferative and apoptotic indices. Bax(-/-) mice did not show increases in proliferation or apoptosis, yet adaptive increases in villus height were enhanced relative to Bax(+/+) mice. Enterocyte migration increased in both genotypes. Postresection, the expression of caspases and genes involved in death receptor-mediated apoptosis was decreased in Bax(-/-) compared with Bax(+/+) mice.
  
  
  CONCLUSIONS
  Postresection adaptation involves parallel changes in crypt proliferation and apoptosis, but, as observed in Bax(-/-) mice, it can occur without increased proliferation. These studies demonstrate that spontaneous gut apoptosis is Bax independent, whereas adaptation-related apoptosis is Bax-dependent. Differences between resected Bax(+/+) and Bax(-/-) mice suggest that apoptosis in the adapting gut utilizes the extrinsic pathway, but this requires linkage to the mitochondrial pathway via Bax. The increased adaptive response in Bax(-/-) mice indicates that modulation of apoptosis may be useful for enhancing adaptation.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Yuzhu
authors.initials: Y
authors.lastname: Tang
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Swartz-Basile
authors.forename: Elzbieta A
authors.initials: EA
authors.lastname: Swietlicki
authors.forename: Lu
authors.initials: L
authors.lastname: Yi
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Rubin
authors.forename: Marc S
authors.initials: MS
authors.lastname: Levin
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002455:Cell Division; D002465:Cell Movement; D015870:Gene Expression; D007421:Intestine, Small / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008871:Microvilli / Q000473:pathology; D011184:Postoperative Period; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D013997:Time Factors; D051028:bcl-2-Associated X Protein
chemical_list: C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; D051028:bcl-2-Associated X Protein