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Early acquisition of bowel segment-specific Bcl-2 homolog expression profiles during development of the human ileum and colon

    1. [1] CIHR Group on the Functional Development and Physiopathology of the Digestive Tract, Department of Anatomy and Cell Biology, Faculty of Medecine, University of Sherbrooke, Sherbrooke, ac, Canada; Research Group on Digestive Physiopathology of the Center of Clinical Research of the CHUS, Fleurimont, ac, Canada
    2. [2] CIHR Group on the Functional Development and Physiopathology of the Digestive Tract, Department of Anatomy and Cell Biology, Faculty of Medecine, University of Sherbrooke, Sherbrooke, ac, Canada
    3. [3] The Burnham Institute, La Jolla Cancer Research Center, La Jolla, CA, USA
  • Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 16, Nº. 2, 2001, págs. 497-510
  • Idioma: inglés
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  • Resumen
    • The adult small and large intestines display distinct expression profiles of Bcl-2 homologs, known regulators of apoptosis. This i thought to indicate that control mechanisms of intestinal apoptosis are gut segment-specific. Little is known on the expression of Bc l-2 homologs during gut development. In man , intestinal features and functions are acquired largely by mid-gestation (18-20 wks); the question whether segment-specific controls of intestinal apoptosis are also acquired early during development remains open. In the present study, we approached this by investigating the expression of six Bel-2 homologs (Bel-2, Bel-XL, Mel1, Bax, Bak, Bad), and one nonhomologous associated molecule (Bag-I), during development of the human ileum and colon (12-20 wks of gestation). Beginning at 18 wks, we found that the epithelial localization of Bel-2 homologs displayed differential pattern (or gradients) in both the ileum and colon; however, the patterns of some of the homologs differed between the two segments. For instance, Bag-1 and Bcl-2 exh ibited crypt-vi ll us decreasing gradients of ex pres ion in the ileum but not in the colon , whereas Mcl-1 displayed differing compartimentalizations between the two segments.

      Further analyses indicated that the steady-state expression leve ls of Bc l- 2 homologs underwent modulat ions between 12 and 20 wks; however, the observed developmental profiles contrasted significantly between the two segments. For example, Bel-2, Bag-1 and Bak levels increased in the colon, but the levels of these same homo.logs decreased in the il eum.

      Furthermore, by 18-20 wks, we found that the expression levels of each Bcl-2 homo log ana lyzed differed greatly between the ileum and co lon.

      Altogether, these data indicate that the expression of Bcl-2 homologs is modulated differentially during human gut development in order to establish, by midgestation, distinct expression profiles for the small and large intestines. This in turn suggests that gut segmentspecific control mechanisms of human intestinal apoptosis are acquired early during fetal life.


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