Dipeptidyl peptidase expression during experimental colitis in mice

Yazbeck, Roger; Sulda, Melanie; Howarth, Gordon S.; Bleich, André; Raber, Kerstin; Hörsten, Stephan von; Holst, Jens J.; Abbott, Catherine A.

doi:10.1002/ibd.21241

Cited by 47 publications

(41 citation statements)

References 59 publications

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“…After dextran sulfate sodium (DSS) treatment for 6 days to induce colitis, DPP8, but not DPP9, mRNA, and enzyme activity is elevated in the colons of both wild-type and DPPIV knockout mice (79), with inhibition of DPP activity impairing neutrophil infiltration at the site of inflammation (79). These data implicate DPP8 in the inflammatory response in colitis.…”

Section: Dpp8 and Dpp9 In The Inflammatory Responsementioning

confidence: 99%

Advances in Understanding the Expression and Function of Dipeptidyl Peptidase 8 and 9

Zhang

Chen

Keane

et al. 2013

Molecular Cancer Research

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DPP8 and DPP9 are recently identified members of the dipeptidyl peptidase IV (DPPIV) enzyme family, which is characterized by the rare ability to cleave a post-proline bond two residues from the N-terminus of a substrate. DPP8 and DPP9 have unique cellular localization patterns, are ubiquitously expressed in tissues and cell lines, and evidence suggests important contributions to various biological processes including: cell behavior, cancer biology, disease pathogenesis, and immune responses. Importantly, functional differences between these two proteins have emerged, such as DPP8 may be more associated with gut inflammation whereas DPP9 is involved in antigen presentation and intracellular signaling. Similarly, the DPP9 connections with H-Ras and SUMO1, and its role in AKT1 pathway downregulation provide essential insights into the molecular mechanisms of DPP9 action. The recent discovery of novel natural substrates of DPP8 and DPP9 highlights the potential role of these proteases in energy metabolism and homeostasis. This review focuses on the recent progress made with these post-proline dipeptidyl peptidases and underscores their emerging importance.

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Section: Dpp8 and Dpp9 In The Inflammatory Responsementioning

confidence: 99%

Advances in Understanding the Expression and Function of Dipeptidyl Peptidase 8 and 9

Zhang

Chen

Keane

et al. 2013

Molecular Cancer Research

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“…Studies utilizing nonselective DP 7 inhibitors (5) and more selective DP8/DP9 inhibitors (6–8) have suggested an important immunological role for DP8/DP9. DP8/DP9 have also been implicated in the allergic response of the lung (9) and inflammatory bowel disorders (10). In vitro studies have demonstrated nonenzymatic roles for DP8 and DP9 in cell migration, proliferation, and apoptosis (11).…”

Section: Introductionmentioning

confidence: 99%

Identifying Natural Substrates for Dipeptidyl Peptidases 8 and 9 Using Terminal Amine Isotopic Labeling of Substrates (TAILS) Reveals in Vivo Roles in Cellular Homeostasis and Energy Metabolism

Wilson

Indarto

Doucet

et al. 2013

Journal of Biological Chemistry

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Background: Biological roles for intracellular dipeptidyl peptidases 8 and 9 are unknown.Results: By degradomics, 29 new in vivo substrates were identified (nine validated) for DP8/DP9, including adenylate kinase 2 and calreticulin.Conclusion: These substrates indicate roles for DP8 and DP9 in metabolism and energy homeostasis.Significance: Being the first proteomics screen for DP8/DP9 substrates, unexpected new cellular roles were revealed.

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“…Given the beneficial effects of GLP-2, it has been studied in multiple GI diseases, including inflammatory bowel disease (IBD) and short bowel syndrome (SBS). In patients with IBD, circulating GLP-2 has been shown to be increased in patients with active disease (17), whereas animal models have found that either providing exogenous GLP-2 (18) or blocking degradation (19) reduces clinical and histological manifestations in experimental colitis. Vasoactive intestinal peptide (VIP), a secreted factor involved in intestinal motility, has been identified as the signal mediator for the anti-inflammatory actions of GLP-2 in rodent colitis models (20,21).…”

mentioning

confidence: 99%

GLP‐2 Delays but Does Not Prevent the Onset of Necrotizing Enterocolitis in Preterm Pigs

Benight

Stoll

Holst

et al. 2013

J. pediatr. gastroenterol. nutr.

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Objectives Necrotizing enterocolitis (NEC) is complex disease thought to occur as a result of an immaturity of the gastrointestinal tract of preterm infants. Intestinal dysfunction induced by total parental nutrition (TPN) may increase the risk for NEC upon introduction of enteral feeding. We hypothesized that the intestinal trophic and anti-inflammatory actions previously ascribed to the gut hormone, glucagon-like peptide-2 (GLP-2), would reduce the incidence of NEC when given in combination with TPN in preterm piglets. Methods Preterm, newborn piglets were nourished by TPN and infused continuously with either human GLP-2 (100 μg · kg−1 · day−1) or control saline for 2 days (n = 12/group). On day 3, TPN was discontinued and pigs were given orogastric formula feeding every 3 hours, and continued GLP-2 or control treatment until the onset of clinical signs of NEC for an additional 96 hours and tissue was collected for molecular and histological endpoints. Results GLP-2 treatment delayed the onset of NEC but was unable to prevent a high NEC incidence (~70%) and severity that occurred in both groups. GLP-2–treated pigs had less histological injury and increased proximal intestinal weight and mucosal villus height, but not crypt depth or Ki-67–positive cells. Inflammatory markers of intestinal myeloperoxidase were unchanged and serum amyloid A levels were higher in GLP-2–treated pigs. Conclusions GLP-2 did not prevent NEC and a proinflammatory response despite some reduction in mucosal injury and increased trophic effect.

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Dipeptidyl peptidase expression during experimental colitis in mice

Cited by 47 publications

References 59 publications

Advances in Understanding the Expression and Function of Dipeptidyl Peptidase 8 and 9

Advances in Understanding the Expression and Function of Dipeptidyl Peptidase 8 and 9

Identifying Natural Substrates for Dipeptidyl Peptidases 8 and 9 Using Terminal Amine Isotopic Labeling of Substrates (TAILS) Reveals in Vivo Roles in Cellular Homeostasis and Energy Metabolism

GLP‐2 Delays but Does Not Prevent the Onset of Necrotizing Enterocolitis in Preterm Pigs

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