Sonic Hedgehog contributes to gastric mucosal restitution after injury

Chang Xiao, Rui Feng, Amy C. Engevik, Jason R. Martin, Julie A. Tritschler, Michael Schumacher, Robert Koncar, Joseph Roland, Ki Taek Nam, James R. Goldenring, Yana Zavros

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Eradication of Helicobacter pylori correlates with regeneration of the gastric epithelium, ulcer healing and re-expression of the gastric morphogen Sonic Hedgehog (Shh). We sought to identify the role of Shh as a regulator of gastric epithelial regeneration during wound healing. A mouse model expressing a parietal cell-specific, tamoxifen-inducible deletion of Shh (HKCre ERT2;Shh flox/flox or PC-iShhKO) was developed. Stomachs were collected and compared 7-150 days after the final vehicle or tamoxifen injection. Ulcers were induced in both controls and PC-iShhKO mice using acetic acid and ulcer size compared 1 and 7 days post induction. (1) Re-expression of Shh correlates with decreased hyperproliferation: Compared to controls, PC-iShhKO mice developed foveolar hyperplasia. Restoration of normal gastric epithelial architecture and differentiation correlated with the re-expression of Shh in PC-iShhKO mice 150 days after the final tamoxifen injection. At the tamoxifen dose used to induce Cre recombination there was no genotoxicity reported in either HKCre ERT2 or Shh flox/flox control mouse stomachs. (2) Delayed wound healing in PC-iShhKO mouse stomachs: To identify the role of Shh in gastric regeneration, an acetic acid ulcer was induced in control and PC-iShhKO mice. Ulcers began to heal in control mice by 7 days after induction. Ulcer healing was documented by decreased ulcer size, angiogenesis, macrophage infiltration and formation of granulation tissue that correlated with the re-expression of Shh within the ulcerated tissue. PC-iShhKO mice did not show evidence of ulcer healing. Re-expression of Shh contributes to gastric regeneration. Our current study may have clinical implications given that eradication of H. pylori correlates with re-expression of Shh, regeneration of the gastric epithelium and ulcer healing.

Original languageEnglish
Pages (from-to)96-111
Number of pages16
JournalLaboratory Investigation
Volume93
Issue number1
DOIs
Publication statusPublished - 2013 Jan 1

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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    Xiao, C., Feng, R., Engevik, A. C., Martin, J. R., Tritschler, J. A., Schumacher, M., Koncar, R., Roland, J., Nam, K. T., Goldenring, J. R., & Zavros, Y. (2013). Sonic Hedgehog contributes to gastric mucosal restitution after injury. Laboratory Investigation, 93(1), 96-111. https://doi.org/10.1038/labinvest.2012.148