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The role of Sonic Hedgehog as a regulator of adult stomach physiology

Xiao, Chang
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307442900

Abstract Details

2011, PhD, University of Cincinnati, Medicine: Systems Biology and Physiology.
Significance: Understanding the role of Sonic Hedgehog (Shh) as a regulator of adult stomach physiology and identifying the underlying mechanism are important for obtaining knowledge of the pathogenesis of Helicobacter pylori (H.pylori) and developing innovative genetic or pharmacologic therapeutic strategies to prevent gastric precancerous transformation. Background: Based on the correlation between loss of Shh and pre-cancerous transformation in the gastric mucosa during H.pylori infection, it is hypothesized that Shh functions as a morphogen in the adult stomach to control the normal function and differentiation of gastric epithelium. However, the physiological consequences of loss of Shh, independent of H.pylori –induced inflammation, remain unexplored. Objectives: Objectives that are met in this dissertation are as follows: (1) Create and characterize tissue specific-Shh deficient mouse models for studying the role of Shh in the homeostasis of gastric epithelium, (2) Identify the cellular and molecular events subsequent to Hedgehog signaling inhibition in both mouse models and cell culture systems, (3) Determine whether Hedgehog signaling is required for tissue regeneration and repair in injured gastric mucosa. Results: Constitutive deletion of Shh from parietal cells resulted in development of gastric hypochlorhydria, hypergastrinemia, foveolar hyperplasia and delayed zymogen cell differentiation. Deletion of Shh caused repressed E-cadherin expression, disrupted adherens- and tight-junctions formation and subsequent activation of Wnt pathway, which may account for the observed phenotype. The clinical process of loss-and regain- of Shh expression during H.pylori infection and eradication was recapitulated in tamoxifen-inducible parietal cell-specific Shh deficient mice, in which re-expression of Shh contributed to the histological restoration of gastric epithelium. Deletion of Shh also impaired the capacity of tissue regeneration and resulted in deficient ulcer healing in the adult stomach. Conclusions: Shh functions as a morphogen in the adult stomach regulating the differentiation and regeneration of gastric epithelium.
Yana Zavros, PhD (Committee Chair)
Simon Hogan, PhD (Committee Member)
Nelson Horseman, PhD (Committee Member)
Marshall Montrose, PhD (Committee Member)
Roger Worrell, PhD (Committee Member)
219 p.
Physiological Psychology
Sonic Hedgehog; adult stomach; differentiation; tissue regeneration

Recommended Citations

Citations

  • Xiao, C. (2011). The role of Sonic Hedgehog as a regulator of adult stomach physiology [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307442900

    APA Style (7th edition)

  • Xiao, Chang. The role of Sonic Hedgehog as a regulator of adult stomach physiology. 2011. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307442900.

    MLA Style (8th edition)

  • Xiao, Chang. "The role of Sonic Hedgehog as a regulator of adult stomach physiology." Doctoral dissertation, University of Cincinnati, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307442900

    Chicago Manual of Style (17th edition)

ucin1307442900
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© 2011, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.