ArticleClinical and experimental gastroenterology2014
Therapeutic treatment with a novel hypoxia-inducible factor hydroxylase inhibitor (TRC160334) ameliorates murine colitis.
Article in Clinical and experimental gastroenterology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Fundamental role for the creatine kinase pathway in protection from murine colitis.Mucosal immunology · 2023Article
- Bacterial Lysate from the Multi-Strain Probiotic SLAB51 Triggers Adaptative Responses to Hypoxia in Human Caco-2 Intestinal Epithelial Cells under Normoxic Conditions and Attenuates LPS-Induced Inflammatory Response.International journal of molecular sciences · 2023Article
- Hypoxia and Intestinal Inflammation: Common Molecular Mechanisms and Signaling Pathways.International journal of molecular sciences · 2023Review
- Article
- Hypoxia inducible factor prolyl hydroxylases in inflammatory bowel disease.Frontiers in pharmacology · 2023Review
- Betulinic acid hydroxamate prevents colonic inflammation and fibrosis in murine models of inflammatory bowel disease.Acta pharmacologica Sinica · 2021Article
- The role of mucosal barriers in human gut health.Archives of pharmacal research · 2021Review
- Hypoxia/HIF Modulates Immune Responses.Biomedicines · 2021Review
- Hypoxia and Innate Immunity: Keeping Up with the HIFsters.Annual review of immunology · 2020Review
- Local Stabilization of Hypoxia-Inducible Factor-1α Controls Intestinal InflammationFrontiers in immunology · 2020Article
- Intrarectally administered polaprezinc attenuates the development of dextran sodium sulfate-induced ulcerative colitis in mice.Experimental and therapeutic medicine · 2019Article
- The Hypoxia-Adenosine Link during Intestinal Inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2018Review
- Targeting Hypoxia Signaling for Perioperative Organ Injury.Anesthesia and analgesia · 2018Review
- Regulation of immunity and inflammation by hypoxia in immunological niches.Nature reviews. Immunology · 2017Review
- Intestinal hypoxia and hypoxia-induced signalling as therapeutic targets for IBD.Nature reviews. Gastroenterology & hepatology · 2017Review
- The role of hypoxia in intestinal inflammation.Molecular and cellular pediatrics · 2016Article
- Immunologic Consequences of Hypoxia during Critical Illness.Anesthesiology · 2016Article
- Therapeutic inhibition of prolyl hydroxylase domain-containing enzymes in surgery: putative applications and challenges.Hypoxia (Auckland, N.Z.) · 2015Review
- Pathogenesis of Crohn's disease.F1000prime reports · 2015Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimMucosal healing in inflammatory bowel disease (IBD) can be achieved by improvement of intestinal barrier protection. Activation of hypoxia-inducible factor (HIF) has been identified as a critical factor for barrier protection during mucosal insult and is linked with improvement in symptoms of colitis. Although prophylactic efficacy of HIF hydroxylase inhibitors in murine colitis have been established, its therapeutic efficacy in clinically relevant therapeutic settings have not been established. In the present study we aim to establish therapeutic efficacy of TRC160334, a novel HIF hydroxylase inhibitor, in animal models of colitis.
methodsThe efficacy of TRC160334 was evaluated in two different mouse models of colitis by oral route. A prophylactic efficacy study was performed in a 2,4,6-trinitrobenzene sulfonic acid-induced mouse model of colitis representing human Crohn's disease pathology. Additionally, a therapeutic efficacy study was performed in a dextran sulfate sodium-induced mouse model of colitis, a model simulating human ulcerative colitis.
resultsTRC160334 treatment resulted in significant improvement in disease end points in both models of colitis. TRC160334 treatment resulted into cytoprotective heatshock protein 70 induction in inflamed colon. TRC160334 successfully attenuated the rate of fall in body weight, disease activity index, and macroscopic and microscopic scores of colonic damage leading to overall improvement in study outcome.
conclusionOur findings are the first to demonstrate that therapeutic intervention with a HIF hydroxylase inhibitor ameliorates IBD in disease models. These findings highlight the potential of TRC160334 for its clinical application in the treatment of IBD.
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