Effects of keratin filament disruption on exocrine pancreas-stimulated secretion and susceptibility to injury

Diana M. Toivola, Nam On Ku, Nafisa Ghori, Anson W. Lowe, Sara A. Michie, M. Bishr Omary

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25 Citations (Scopus)


Disruption or absence of hepatocyte keratins 8 and 18 is associated with chronic hepatitis, marked hepatocyte fragility, and a significant predisposition to stress-induced liver injury. In contrast, pancreatic keratin disruption in transgenic mice that express keratin 18 Arg89 → Cys (K18C) is not associated with an obvious pancreatic pathology. We compared the effects of keratin filament disruption on pancreatic acini or acinar cell viability, and on cholecystokinin (CCK)-stimulated secretion, in transgenic mice that overexpress wild-type keratin 18 and harbor normal extended keratin filaments (TG2) and K18C mice. We also compared the response of these mice to pancreatitis induced by a choline-deficient ethionine-supplemented diet or by caerulein. Despite extensive cytoplasmic keratin filament disruption, the apicolateral keratin filament bundles appear intact in the acinar pancreas of K18C mice, as determined ultrastructurally and by light microscopy. No significant pancreatitis-associated histologic, serologic, or F-actin/keratin apicolateral redistribution differences were noted between TG2 and K18C mice. Acinar cell viability and yield after collagenase digestion were lower in K18C than in TG2 mice, but the yields of intact acini and their 125I-CCK uptake and responses to CCK-stimulated secretion were similar. Our results indicate that keratin filament reorganization is a normal physiologic response to pancreatic cell injury, but an intact keratin cytoplasmic filament network is not as essential in protection from cell injury as in the liver. These findings raise the possibility that the abundant apicolateral acinar keratin filaments, which are not as evident in hepatocytes, may play the cytoprotective role that is seen in liver and other tissues. Alternatively, identical keratins may function differently in different tissues. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)156-170
Number of pages15
JournalExperimental Cell Research
Issue number2
Publication statusPublished - 2000 Mar 15

Bibliographical note

Funding Information:
We are grateful to Robert Oshima (The Burnham Institute, La Jolla, CA) for the use of the TG2 mice and for the anti-mouse K18 antibody, Harald Herrmann (German Cancer Research Center, Heidelberg, Germany) for the plectin antibody, John Williams (University of Michigan) and Guy Groblewski (University of Wisconsin, Madison) for advice regarding acinar cell preparations, Evelyn Z. Resurreccion for assistance with immunofluorescence staining, Roy Soetikno for help with statistical analysis, Kris Morrow for preparing the figures, Li Feng for assistance with some of the experiments, Marta Raygoza for animal breeding and care, and Steve Avolicino for the histology staining. This work was supported by Veterans Administration Merit and Career Development Awards, NIH Grant DK52951, Digestive Disease Center Grant DK38707, and a Postdoctoral Fellowship from The Academy of Finland to D. M. Toivola.

All Science Journal Classification (ASJC) codes

  • Cell Biology


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