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TRPV6 channel mediates alcohol-induced gut barrier dysfunction and systemic response
Avtar S Meena1, Pradeep K Shukla1, Briar Bell1
1Departments of Physiology, Medicine, Molecular Biology Immunology & Biochemistry, and Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Cell Reports
|June 15, 2022
Summary
Alcohol disrupts the gut barrier by increasing intracellular calcium via TRPV6 channels. Inhibiting TRPV6 protects against alcohol-induced gut dysfunction and inflammation, offering therapeutic potential.
Area of Science:
- Gastroenterology
- Cell Biology
- Toxicology
Background:
- Intestinal tight junction disruption is key to alcohol-associated organ damage.
- Ethanol and acetaldehyde elevate intracellular calcium, impairing gut barrier function.
Purpose of the Study:
- Identify the calcium channel responsible for alcohol-induced gut barrier dysfunction.
- Investigate TRPV6 as a mediator of alcohol's effects on the intestine.
Main Methods:
- Utilized Caco-2 cell monolayers and mouse intestinal organoids.
- Assessed the impact of TRPV6 deficiency or inhibition on calcium influx and barrier integrity.
- Employed photoaffinity labeling to identify alcohol-binding sites on TRPV6.
Main Results:
- Ethanol and acetaldehyde activate TRPV6, increasing intracellular calcium and disrupting tight junctions.
- TRPV6 deficiency or inhibition prevented alcohol-induced barrier dysfunction in vitro and in vivo.
- Identified a potential alcohol-binding site involving histidine and arginine residues in TRPV6.
Conclusions:
- TRPV6 is essential for alcohol-induced intestinal barrier dysfunction and systemic inflammation.
- Targeting TRPV6 function may mitigate alcohol-associated tissue injury.
Keywords:
CP: Cell biologyCP: ImmunologyTRPValcoholalcohol-binding sitecalciumendotoxemiaintestineliverneuroinflammationsystemic inflammationtight junctionMore Related Videos
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