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

Scoggins CR, Meszoely IM, Wada M, Means AL, Yang L, Leach SD
Am J Physiol Gastrointest Liver Physiol. 2000 279 (4): G827-36

PMID: 11005771 · DOI:10.1152/ajpgi.2000.279.4.G827

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(WAF1/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.

MeSH Terms (18)

Animals Apoptosis bcl-2-Associated X Protein Cyclin-Dependent Kinase Inhibitor p21 Cyclins Epithelial Cells Female Male Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Knockout Pancreas Pancreatic Ducts Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Time Factors Tumor Suppressor Protein p53

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