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Updated: Oct 13, 2025

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Calcium-sensing receptor protects intestinal integrity and alleviates the inflammatory response via the Rac1/PLCγ1

Guangmang Liu1,2,3, Jie Zheng1,2,3, Ke Gu1,2,3

  • 1Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, China.

Animal Biotechnology
|November 11, 2021
PubMed

Insights

Activation of the calcium-sensing receptor (CaSR) preserves intestinal barrier integrity and reduces inflammation by modulating the Rac1/PLC-γ1 pathway. Spermine maintains barrier function via this CaSR pathway.

Area of Science:

  • Gastroenterology
  • Cell Biology
  • Molecular Signaling

Background:

  • Intestinal epithelial barrier integrity is crucial for gut health.
  • Inflammatory responses can compromise barrier function.
  • The calcium-sensing receptor (CaSR) role in intestinal barrier regulation is under investigation.

Purpose of the Study:

  • To investigate the protective role of CaSR in intestinal epithelial barrier integrity.
  • To determine the involvement of the Ras-related C3 botulinum toxin substrate 1 (Rac1)/phospholipase Cγ1 (PLC-γ1) signaling pathway.
  • To examine the effect of spermine on CaSR-mediated barrier function.

Main Methods:

  • Utilized IPEC-J2 cell monolayers.
  • Applied TNF-α to induce inflammation.
  • Manipulated CaSR activity (antagonist NPS 2143, overexpression).
  • Silenced Rac1 and PLCγ1.
  • Administered spermine.

Main Results:

  • Spermine enhanced barrier function (TER, tight junctions) and reduced permeability under TNF-α challenge.
  • CaSR overexpression increased barrier integrity and decreased inflammatory markers (IL-8, TNF-α).
  • Rac1 and PLCγ1 silencing abrogated CaSR-mediated protective effects.

Conclusions:

  • CaSR activation protects intestinal integrity and reduces inflammation via the Rac1/PLC-γ1 pathway.
  • Spermine maintains intestinal barrier function through CaSR/Rac1/PLC-γ1 signaling.
  • CaSR represents a potential therapeutic target for inflammatory gut conditions.
Keywords:
Calcium-sensing receptorPLCγ1Rac1barrier functionrepair of intestinal damage

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