Hedgehog signaling regulates E-cadherin expression for the maintenance of the actin cytoskeleton and tight junctions

Chang Xiao, Sally A. Ogle, Michael A. Schumacher, Neal Schilling, Robert A. Tokhunts, Melissa A. Orr-Asman, Marian L. Miller, David J Robbins, Frederic Hollande, Yana Zavros

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

In the stomach, strictly regulated cell adherens junctions are crucial in determining epithelial cell differentiation. Sonic Hedgehog (Shh) regulates epithelial cell differentiation in the adult stomach. We sought to identify whether Shh plays a role in regulating adherens junction protein E-cadherin as a mechanism for epithelial cell differentiation. Mouse nontumorigenic gastric epithelial (IMGE-5) cells treated with Hedgehog signaling inhibitor cyclopamine and anti-Shh 5E1 antibody or transduced with short hairpin RNA against Skinny Hedgehog (IMGE-5Ski) were cultured. A mouse model expressing a parietal cell-specific deletion of Shh (HKCre/ShhKO) was used to identify further changes in adherens and tight junctions. Inhibition of Hedgehog signaling in IMGE-5 cells caused loss of E-cadherin expression accompanied by disruption of F-actin cortical expression and relocalization of zonula occludens-1 (ZO-1). Loss of E-cadherin was also associated with increased proliferation in IMGE-5Ski cells and increased expression of the mucous neck cell lineage marker MUC6. Compared with membrane-expressed E-cadherin and ZO-1 protein in controls, dissociation of E-cadherin/β- catenin and ZO-1/occludin protein complexes was observed in HKCre/Shh KO mice. In conclusion, we demonstrate that Hedgehog signaling regulates E-cadherin expression that is required for the maintenance of F-actin cortical expression and stability of tight junction protein ZO-1.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume299
Issue number6
DOIs
StatePublished - Dec 1 2010

Fingerprint

Hedgehogs
Tight Junctions
Cadherins
Actin Cytoskeleton
Maintenance
Adherens Junctions
Zonula Occludens-1 Protein
Cell Differentiation
Stomach
Epithelial Cells
Actins
Occludin
Tight Junction Proteins
Catenins
Intercellular Junctions
Cell Lineage
Small Interfering RNA
Neck
Membranes
Antibodies

Keywords

  • Epithelial-to-mesenchymal-transition
  • IMGE-5 cells
  • Zonula occludens-1

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

Cite this

Hedgehog signaling regulates E-cadherin expression for the maintenance of the actin cytoskeleton and tight junctions. / Xiao, Chang; Ogle, Sally A.; Schumacher, Michael A.; Schilling, Neal; Tokhunts, Robert A.; Orr-Asman, Melissa A.; Miller, Marian L.; Robbins, David J; Hollande, Frederic; Zavros, Yana.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 299, No. 6, 01.12.2010.

Research output: Contribution to journalArticle

Xiao, Chang ; Ogle, Sally A. ; Schumacher, Michael A. ; Schilling, Neal ; Tokhunts, Robert A. ; Orr-Asman, Melissa A. ; Miller, Marian L. ; Robbins, David J ; Hollande, Frederic ; Zavros, Yana. / Hedgehog signaling regulates E-cadherin expression for the maintenance of the actin cytoskeleton and tight junctions. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2010 ; Vol. 299, No. 6.
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