p53-dependent acinar cell apoptosis triggers epithelial proliferation in duct-ligated murine pancreas

Charles R. Scoggins, Ingrid M. Meszoely, Michihiko Wada, Anna L. Means, Liying Yang, Steven D. Leach

Research output: Contribution to journalArticlepeer-review

Abstract

The mechanisms linking acinar cell apoptosis and ductal epithelial proliferation remain unknown. To determine the relationship between these events, pancreatic duct ligation (PDL) was performed on p53(+/+) and p53(-/-) mice. In mice bearing a wild-type p53 allele, PDL resulted in upregulation of p53 protein in both acinar cells and proliferating duct-like epithelium. In contrast, upregulation of Bcl-2 occurred only in duct-like epithelium. Both p21(WAE1/CIP1) and Bax were also upregulated in duct-ligated lobes. After PDL in p53(+/+) mice, acinar cells underwent widespread apoptosis, while duct-like epithelium underwent proliferative expansion. In the absence of p53, upregulation of p53 target genes and acinar cell apoptosis did not occur. The absence of acinar cell apoptosis in p53(-/-) mice also eliminated the proliferative response to duct ligation. These data demonstrate that PDL-induced acinar cell apoptosis is a p53-dependent event and suggest a direct link between acinar cell apoptosis and proliferation of duct-like epithelium in duct-ligated pancreas.

Original languageEnglish (US)
Pages (from-to)G827-G836
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume279
Issue number4 42-4
DOIs
StatePublished - 2000

Keywords

  • Bax
  • Bcl-2
  • Duct ligation
  • P21
  • Regeneration

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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