Epithelial CaSR deficiency alters intestinal integrity and promotes proinflammatory immune responses

Sam X. Cheng, Yaíma L. Lightfoot, Tao Yang, Mojgan Zadeh, Lieqi Tang, Bikash Sahay, Gary P. Wang, Jennifer L. Owen, Mansour Mohamadzadeh

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

The intestinal epithelium is equipped with sensing receptor mechanisms that interact with luminal microorganisms and nutrients to regulate barrier function and gut immune responses, thereby maintaining intestinal homeostasis. Herein, we clarify the role of the extracellular calcium-sensing receptor (CaSR) using intestinal epithelium-specific Casr-/- mice. Epithelial CaSR deficiency diminished intestinal barrier function, altered microbiota composition, and skewed immune responses towards proinflammatory. Consequently, Casr-/- mice were significantly more prone to chemically induced intestinal inflammation resulting in colitis. Accordingly, CaSR represents a potential therapeutic target for autoinflammatory disorders, including inflammatory bowel diseases.

Original languageEnglish (US)
Pages (from-to)4158-4166
Number of pages9
JournalFEBS Letters
Volume588
Issue number22
DOIs
StatePublished - Nov 17 2014
Externally publishedYes

Keywords

  • Calcium-sensing receptor
  • Colitis
  • Epithelial cell
  • Gut microbiota
  • Inflammation
  • Intestinal barrier function

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biophysics
  • Structural Biology
  • Biochemistry
  • Cell Biology

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