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Hedgehog Signaling is a Mediator of the Gastric Immune Response to Helicobacter pylori Infection

Schumacher, Michael A
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1394725492

Abstract Details

2014, PhD, University of Cincinnati, Medicine: Systems Biology and Physiology.
Significance: Helicobacter pylori (H. pylori) infection causes gastric inflammation and is associated with the development of gastric disease. To prevent severe disease occurrence it is essential to determine what bacterial or host factors play a role in the pathogenesis of the organism. The role of Sonic Hedgehog (Shh) in mediating gastric inflammatory disease has not been studied. This lack of knowledge of the acute immune mechanisms underlying H. pylori infection obstructs our understanding of H. pylori persistence and associated disease development. This knowledge will aid in determining dysregulated gastric signaling mechanisms and may be useful as a predictive marker for identifying those at risk to develop severe outcomes associated with H. pylori infection. Background: H. pylori infection regulates expression of Shh in gastric tissue, which may contribute to the persistence and pathogenesis of the bacteria. Objectives: The objectives of this dissertation are to: (1) Identify the acute mechanism by which H. pylori regulates Shh expression in the gastric tissue, (2) Determine the role of Shh in mediating gastric inflammation in response to H. pylori infection, and (3) Identify the mechanism by which Shh mediates H. pylori-induced gastric inflammation. Results: Acute H. pylori infection induces Shh expression in and secretion from the parietal cells of the stomach via an NF?B-mediated mechanism. Secreted Shh elicits macrophage recruitment to the gastric tissue within 2 days post-infection to initiate and potentiate the gastric inflammatory response to H. pylori. Shh-stimulated macrophage recruitment is dependent upon expression of the Hedgehog signal transducer, Smoothened, in macrophages. Conclusions: This dissertation identified the novel finding that acute H. pylori infection induces Shh expression and secretion; an effect that is crucial for macrophage recruitment and subsequently the initiation and establishment of the gastric immune response. Loss of Shh following chronic infection in the gastric tissue represents a disruption of the immune mechanisms that may be instrumental in eradicating bacterial infection, thus enabling H. pylori persistence and disease development.
Yana Zavros, Ph.D. (Committee Chair)
De'Broski Rafael Herbert, Ph.D. (Committee Member)
Simon Hogan, Ph.D. (Committee Member)
Danuta Malinowska, Ph.D. (Committee Member)
Marshall Montrose, Ph.D. (Committee Member)
224 p.
Physiological Psychology
sonic hedgehog; helicobacter; organoid; inflammation; macrophage; smoothened

Recommended Citations

Citations

  • Schumacher, M. A. (2014). Hedgehog Signaling is a Mediator of the Gastric Immune Response to Helicobacter pylori Infection [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1394725492

    APA Style (7th edition)

  • Schumacher, Michael. Hedgehog Signaling is a Mediator of the Gastric Immune Response to Helicobacter pylori Infection. 2014. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1394725492.

    MLA Style (8th edition)

  • Schumacher, Michael. "Hedgehog Signaling is a Mediator of the Gastric Immune Response to Helicobacter pylori Infection." Doctoral dissertation, University of Cincinnati, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1394725492

    Chicago Manual of Style (17th edition)

ucin1394725492
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This open access ETD is published by University of Cincinnati and OhioLINK.