p53-dependent acinar cell apoptosis triggers epithelial proliferation in duct-ligated murine pancreas
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...
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| Veröffentlicht in: | American journal of physiology: Gastrointestinal and liver physiology 2000-10, Vol.279 (4), p.G827-G836 |
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| container_issue | 4 |
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| container_title | American journal of physiology: Gastrointestinal and liver physiology |
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| creator | Scoggins, C R Meszoely, I M Wada, M Means, A L Yang, L Leach, S D |
| description | 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. |
| doi_str_mv | 10.1152/ajpgi.2000.279.4.g827 |
| format | Article |
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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. 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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.</description><subject>Animals</subject><subject>Apoptosis - physiology</subject><subject>bcl-2-Associated X Protein</subject><subject>Cyclin-Dependent Kinase Inhibitor p21</subject><subject>Cyclins - analysis</subject><subject>Epithelial Cells - cytology</subject><subject>Female</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred DBA</subject><subject>Mice, Knockout</subject><subject>Pancreas - cytology</subject><subject>Pancreatic Ducts - physiology</subject><subject>Proto-Oncogene Proteins - analysis</subject><subject>Proto-Oncogene Proteins c-bcl-2</subject><subject>Time Factors</subject><subject>Tumor Suppressor Protein p53 - deficiency</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - physiology</subject><issn>0193-1857</issn><issn>1522-1547</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEFv2zAMhYViQ5tl_QkbdNrNninZln0sijUdEGCX7SxQMu0qcGxVkg_791PaADuRAN8jHz_GvkBVAjTiO5785EpRVVUpVF_W5dQJdcN2eSYKaGr1ge0q6GUBXaPu2KcYT1nbCIBbdgeQW6Vgx8g3shjI0zLQkjhat2DgluaZo199WqOLPAU3TRQiJ-_SC80OZ-7DOruRAia3LtwtfNhsKmY3YaKBn7fgFuIeFxsI42f2ccQ50v217tmfpx-_H5-L46_Dz8eHY2GlglQMOBpj5WCUIYMGAXprsG8rWY1GDIRd31jbdp2oYezHVoEUWKuuVm0rR9vLPfv2vjene90oJn128fIMLrRuUSsh-kxLZWHzLrRhjTHQqH1wZwx_NVT6wle_8dUXvjo7dK0PmW_2fb0e2MyZhv-uK1D5D4wqeso</recordid><startdate>20001001</startdate><enddate>20001001</enddate><creator>Scoggins, C R</creator><creator>Meszoely, I M</creator><creator>Wada, M</creator><creator>Means, A L</creator><creator>Yang, L</creator><creator>Leach, S D</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20001001</creationdate><title>p53-dependent acinar cell apoptosis triggers epithelial proliferation in duct-ligated murine pancreas</title><author>Scoggins, C R ; Meszoely, I M ; Wada, M ; Means, A L ; Yang, L ; Leach, S D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c371t-dafbbc3db7bebaba119cba96030fb2dea895cc688241f9f67132a47847663fc93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Apoptosis - physiology</topic><topic>bcl-2-Associated X Protein</topic><topic>Cyclin-Dependent Kinase Inhibitor p21</topic><topic>Cyclins - analysis</topic><topic>Epithelial Cells - cytology</topic><topic>Female</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred DBA</topic><topic>Mice, Knockout</topic><topic>Pancreas - cytology</topic><topic>Pancreatic Ducts - physiology</topic><topic>Proto-Oncogene Proteins - analysis</topic><topic>Proto-Oncogene Proteins c-bcl-2</topic><topic>Time Factors</topic><topic>Tumor Suppressor Protein p53 - deficiency</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Scoggins, C R</creatorcontrib><creatorcontrib>Meszoely, I M</creatorcontrib><creatorcontrib>Wada, M</creatorcontrib><creatorcontrib>Means, A L</creatorcontrib><creatorcontrib>Yang, L</creatorcontrib><creatorcontrib>Leach, S D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of physiology: Gastrointestinal and liver physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Scoggins, C R</au><au>Meszoely, I M</au><au>Wada, M</au><au>Means, A L</au><au>Yang, L</au><au>Leach, S D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>p53-dependent acinar cell apoptosis triggers epithelial proliferation in duct-ligated murine pancreas</atitle><jtitle>American journal of physiology: Gastrointestinal and liver physiology</jtitle><addtitle>Am J Physiol Gastrointest Liver Physiol</addtitle><date>2000-10-01</date><risdate>2000</risdate><volume>279</volume><issue>4</issue><spage>G827</spage><epage>G836</epage><pages>G827-G836</pages><issn>0193-1857</issn><eissn>1522-1547</eissn><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(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.</abstract><cop>United States</cop><pmid>11005771</pmid><doi>10.1152/ajpgi.2000.279.4.g827</doi></addata></record> |
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| source | MEDLINE; American Physiological Society; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Apoptosis - physiology bcl-2-Associated X Protein Cyclin-Dependent Kinase Inhibitor p21 Cyclins - analysis Epithelial Cells - cytology Female Male Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Knockout Pancreas - cytology Pancreatic Ducts - physiology Proto-Oncogene Proteins - analysis Proto-Oncogene Proteins c-bcl-2 Time Factors Tumor Suppressor Protein p53 - deficiency Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - physiology |
| title | p53-dependent acinar cell apoptosis triggers epithelial proliferation in duct-ligated murine pancreas |
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