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Updated: May 5, 2026
In vitro Functional Characterization of Mouse Colorectal Afferent Endings
Published on: January 21, 2015
Transient receptor potential vanilloid 4 activated inflammatory signals by intestinal epithelial cells and colitis in
Emilie D'Aldebert1, Nicolas Cenac, Perrine Rousset
1INSERM Unité 563 Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
Background & Aims:
Ligand-gated calcium channels have been reported to be involved in the pathogenesis of inflammatory bowel disease. One family member, transient receptor potential vanilloid 4 (TRPV4), is activated by arachidonic acid derivatives that might be released on inflammation, yet its role in gastrointestinal inflammation has not been characterized. We investigated whether TRPV4 activation participates in intestinal inflammation and its expression and functions in the gastrointestinal tract.
Methods:
TRPV4 expression was studied in human colon samples, human intestinal epithelial cell lines (Caco-2 and T84), and inflamed colons of mice. Calcium mobilization and cytokine release were analyzed in intestinal epithelial cells exposed to the selective TRPV4 agonist 4α-phorbol-12,13-didecanoate (4αPDD). Mice were killed 3, 6, or 24 hours after intracolonic administration of 4αPDD; inflammatory parameters were measured in their colon tissues, and paracellular colonic permeability was measured by the passage of (51)Cr-EDTA from the colon lumen to the blood.
Results:
High levels of TRPV4 were detected in Caco-2 cells and in epithelial cells of human colon tissue samples; its expression was up-regulated in colons from inflamed mice compared with noninflamed control mice. Administration of 4αPDD to Caco-2 and T84 cells caused a dose-dependent increase in intracellular calcium concentration and chemokine release. In mice, intracolonic administration of 4αPDD caused colitis to develop 3 to 6 hours later; inflammation resolved by 24 hours. Increased colonic permeability was observed in vivo 3 hours after intracolonic administration of 4αPDD.
Conclusions:
TRPV4 is expressed and functional in intestinal epithelial cells; its activation in the gastrointestinal tract causes increases in intracellular calcium concentrations, chemokine release, and colitis.
Insights
Transient Receptor Potential Vanilloid 4 (TRPV4) is present in the gut and its activation triggers inflammation and increased intestinal permeability. This study shows TRPV4 plays a role in gastrointestinal inflammation.
Area of Science:
- Gastroenterology
- Immunology
- Molecular Biology
Background:
- Ligand-gated calcium channels, including TRPV4, are implicated in inflammatory bowel disease pathogenesis.
- TRPV4 is activated by arachidonic acid derivatives potentially released during inflammation.
- The role of TRPV4 in gastrointestinal inflammation remains uncharacterized.
Purpose of the Study:
- To investigate the role of TRPV4 activation in intestinal inflammation.
- To examine TRPV4 expression and function in the gastrointestinal tract.
Main Methods:
- TRPV4 expression analyzed in human colon samples, Caco-2, and T84 cells, and inflamed mouse colons.
- Calcium mobilization and cytokine release measured in intestinal cells treated with TRPV4 agonist 4αPDD.
- Colitis induced in mice via intracolonic 4αPDD administration; inflammatory parameters and colonic permeability assessed.
Main Results:
- High TRPV4 expression found in human colon epithelial cells and Caco-2 cells; upregulated in inflamed mouse colons.
- 4αPDD induced dose-dependent calcium influx and chemokine release in intestinal cells.
- Intracolonic 4αPDD triggered colitis and increased colonic permeability in mice within hours, resolving by 24 hours.
Conclusions:
- TRPV4 is expressed and functional in intestinal epithelial cells.
- TRPV4 activation in the GI tract increases intracellular calcium, chemokine release, and induces colitis.
- TRPV4 represents a potential therapeutic target for gastrointestinal inflammation.
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