Browsing by Author "Bakke, Danika"

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    AMP peptide targets tight junctions to protect and heal barrier structure and function in models of IBD.
    (Wolters Kluwer, 2015-10) Chen, Peili; Bakke, Danika; Kolodziej, Lauren; Lodolce, James; Weber, Christopher R.; Boone, David L.; Toback, F. Gary; Department of Microbiology and Immunology, IU School of Medicine
    Background: A peptide derived from Antrum Mucosal Protein (AMP)-18 (gastrokine-1) reduces the extent of mucosal erosions and clinical severity in mice with dextran sulfate sodium (DSS)-induced colonic injury. The present study set out to determine if AMP peptide was also therapeutic for immune- and cytokine-mediated mouse models of intestinal injury and inflammatory bowel diseases (IBD) by enhancing and stabilizing tight junctions (TJs). Methods: Therapeutic effects of AMP peptide were examined in interleukin-10 deficient and a T cell adoptive transfer models of colitis in immunodeficient recombinase activating gene-1 knock-out (RAG-1−/−) mice. Mechanisms by which AMP peptide enhances barrier function and structure were studied ex vivo using intestine and colon from mice given lipopolysaccharide (LPS), and in AMP-18 deficient mice given DSS. Results: In interleukin-10 deficient mice given piroxicam, AMP peptide enhanced recovery after weight loss, protected against colon shortening and segmental dilation, and reduced the colitis activity score. In the T cell transfer model, treatment with the peptide protected against colon shortening. In mice given LPS in vivo to induce gut injury, AMP peptide prevented the onset of, and reversed established intestinal hyperpermeability by targeting TJ proteins and perijunctional actin.
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    Gastrokine-1, an anti-amyloidogenic protein secreted by the stomach, regulates diet-induced obesity
    (Springer Nature, 2021-05-04) Overstreet, Anne-Marie C.; Grayson, Bernadette E.; Boger, Antonia; Bakke, Danika; Carmody, Erin M.; Bales, Cayla E.; Paski, Shirley C.; Murphy, Stephen F.; Dethlefs, Christopher R.; Shannon, Kara J.; Adlaka, Katie R.; Wolford, Claire E.; Campiti, Vincent J.; Raghunandan, Christina V.; Seeley, Randy J.; Boone, David L.; Microbiology and Immunology, School of Medicine
    Obesity and its sequelae have a major impact on human health. The stomach contributes to obesity in ways that extend beyond its role in digestion, including through effects on the microbiome. Gastrokine-1 (GKN1) is an anti-amyloidogenic protein abundantly and specifically secreted into the stomach lumen. We examined whether GKN1 plays a role in the development of obesity and regulation of the gut microbiome. Gkn1−/− mice were resistant to diet-induced obesity and hepatic steatosis (high fat diet (HFD) fat mass (g) = 10.4 ± 3.0 (WT) versus 2.9 ± 2.3 (Gkn1−/−) p < 0.005; HFD liver mass (g) = 1.3 ± 0.11 (WT) versus 1.1 ± 0.07 (Gkn1−/−) p < 0.05). Gkn1−/− mice also exhibited increased expression of the lipid-regulating hormone ANGPTL4 in the small bowel. The microbiome of Gkn1−/− mice exhibited reduced populations of microbes implicated in obesity, namely Firmicutes of the class Erysipelotrichia. Altered metabolism consistent with use of fat as an energy source was evident in Gkn1−/− mice during the sleep period. GKN1 may contribute to the effects of the stomach on the microbiome and obesity. Inhibition of GKN1 may be a means to prevent obesity.