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EpCAM (CD326) Regulates Intestinal Epithelial Integrity and Stem Cells via Rho-Associated Kinase.

Takeshi Ouchi1, Sohshi Morimura2, Lukas E Dow3

  • 1Department of Dermatology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-0016, Japan.

Cells
|February 2, 2021
PubMed
Summary
This summary is machine-generated.

Epithelial Cell Adhesion Molecule (EpCAM) deficiency impairs intestinal epithelial integrity and stem cell function. Rho-associated coiled-coil kinase (ROCK) inhibitors partially restored epithelial integrity and increased stem cell numbers in EpCAM-deficient models.

Keywords:
EpCAMROCKorganoidspheroidstem cell

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Area of Science:

  • Gastroenterology and Molecular Biology
  • Cell Biology and Physiology

Background:

  • Congenital tufting enteropathy (CTE) is linked to inactivating mutations in Epithelial Cell Adhesion Molecule (EpCAM).
  • EpCAM's precise role in intestinal epithelial homeostasis remains incompletely understood.

Purpose of the Study:

  • To investigate the mechanistic role of EpCAM in intestinal epithelial cells.
  • To identify potential therapeutic targets for EpCAM-deficiency related disorders.

Main Methods:

  • Generation of EpCAM-deficient intestinal epithelial cell (IEC) organoids and spheroids from ROSA-Cre mice.
  • Assessment of proliferation, tight junctions, cell polarity, epithelial integrity, and stem cell populations (Olfm4+).
  • Screening of pharmacologic inhibitors, including Rho-associated coiled-coil kinase (ROCK) inhibitors, to ameliorate EpCAM deficiency effects.

Main Results:

  • EpCAM deletion led to increased apoptosis, reduced organoid/spheroid growth, destabilized claudins, and compromised epithelial integrity.
  • ROCK inhibitors improved epithelial integrity but did not restore claudin expression.
  • EpCAM deficiency decreased Olfm4-expressing stem cells, an effect reversed by ROCK inhibitor treatment.

Conclusions:

  • EpCAM is crucial for maintaining intestinal epithelial homeostasis.
  • EpCAM signaling involves the Rho-associated coiled-coil kinase (ROCK) pathway.
  • ROCK inhibitors show therapeutic potential for EpCAM-deficiency related enteropathies by improving epithelial integrity and stem cell populations.