Epithelial CaSR deficiency alters intestinal integrity and promotes proinflammatory immune responses

FEBS Lett. 2014 Nov 17;588(22):4158-66. doi: 10.1016/j.febslet.2014.05.007. Epub 2014 May 17.


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.

Keywords: Calcium-sensing receptor; Colitis; Epithelial cell; Gut microbiota; Inflammation; Intestinal barrier function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Colitis / chemically induced
  • Colitis / immunology
  • Colitis / metabolism
  • Colitis / microbiology
  • Dextran Sulfate / adverse effects
  • Gene Knockout Techniques
  • Inflammation / chemically induced
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / microbiology
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Microbiota / drug effects
  • Receptors, Calcium-Sensing / deficiency*
  • Receptors, Calcium-Sensing / genetics
  • Receptors, Calcium-Sensing / metabolism
  • Signal Transduction / drug effects


  • Receptors, Calcium-Sensing
  • Dextran Sulfate