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Development and resolution of experimental colitis in mice with targeted deletion of dipeptidyl peptidase IV

Authors

  • Mark S. Geier,

    1. Child Health Research Institute and Centre for Paediatric and Adolescent Gastroenterology, Women's and Children's Hospital, North Adelaide, South Australia, Australia
    2. Disciplines of Physiology, School of Molecular and Biomedical Sciences, and the Department of Paediatrics, The University of Adelaide, South Australia, Australia
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  • Danik Tenikoff,

    1. Child Health Research Institute and Centre for Paediatric and Adolescent Gastroenterology, Women's and Children's Hospital, North Adelaide, South Australia, Australia
    2. Disciplines of Physiology, School of Molecular and Biomedical Sciences, and the Department of Paediatrics, The University of Adelaide, South Australia, Australia
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  • Roger Yazbeck,

    1. Child Health Research Institute and Centre for Paediatric and Adolescent Gastroenterology, Women's and Children's Hospital, North Adelaide, South Australia, Australia
    2. School of Biological Sciences, Flinders University, Adelaide, South Australia, Australia
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  • Geoffrey W. McCaughan,

    1. A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
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  • Catherine A. Abbott,

    1. School of Biological Sciences, Flinders University, Adelaide, South Australia, Australia
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  • Gordon S. Howarth

    Corresponding author
    1. Child Health Research Institute and Centre for Paediatric and Adolescent Gastroenterology, Women's and Children's Hospital, North Adelaide, South Australia, Australia
    2. Disciplines of Physiology, School of Molecular and Biomedical Sciences, and the Department of Paediatrics, The University of Adelaide, South Australia, Australia
    3. School of Biological Sciences, Flinders University, Adelaide, South Australia, Australia
    4. School of Pharmaceutical, Molecular and Biomedical Sciences, University of South Australia, Australia
    • Child Health Research Institute, 72 King William Road, North Adelaide, South Australia, 5006 Australia.
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  • Catherine A. Abbott and Gordon S. Howarth contributed equally to this study.

Abstract

Glucagon-like peptide-2 (GLP-2) is a potent intestinotrophic growth factor that enhances repair of damaged intestinal tissue. However, its bioactivity is limited by dipeptidyl peptidase IV (DPIV)-mediated degradation. We hypothesized that DPIV−/− mice would display an increased resistance to, and an enhanced recovery from, dextran sulfate sodium (DSS)-induced colitis compared to DPIV+/+ mice. DPIV+/+ and DPIV−/− mice consumed 2% DSS for 6 days, followed by a 15 day recovery period. Mice were killed at days 0, 3, 6, 9, 14, and 21 (n = 6–8) and the small intestine and colon removed for histological assessment of villus height, crypt depth, and crypt area. The epithelial cell proliferative labeling index was determined by proliferating cell nuclear antigen (PCNA) immunostaining. Small intestine, colon, and total body weight did not differ between DPIV+/+ and DPIV−/− mice. Distal colon crypt depth did not differ significantly between DPIV+/+ and DPIV−/− mice during the development of DSS-colitis or during the recovery phase. Similarly no significant effects were apparent on distal colon crypt area or PCNA labeling index between DPIV+/+ and DPIV−/− during the development of and recovery from DSS-colitis. However, DPIV−/− mice still possessed significant levels of plasma DPIV-like activity. We conclude that loss of DPIV activity does not increase resistance to experimental colitis and hypothesize that other DPIV family members may also be involved in the cleavage of GLP-2. © 2005 Wiley-Liss, Inc.

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