# TRPA1 Expressed by Hepatocytes and Liver Macrophages Does Not Mediate Inflammatory Infiltration and Steatosis in a Mouse Model of Chronic Alcohol-Induced Liver Injury

## TL;DR

This study shows that TRPA1 is present in liver cells and activated by alcohol byproducts, but it does not cause liver inflammation or fat buildup from chronic alcohol use in mice.

## Contribution

The study demonstrates that TRPA1 is expressed in hepatocytes and macrophages but does not mediate alcohol-induced liver damage in mice.

## Key findings

- Trpa1 mRNA is expressed in mouse hepatocytes and liver macrophages.
- Acetaldehyde activates human TRPA1.
- Chronic alcohol-induced liver steatosis and inflammation occur independently of TRPA1.

## Abstract

Using RNAscope ISH, we prove Trpa1 mRNA expression in hepatocytes and liver macrophages. We confirm that acetaldehyde is capable of activating human TRPA1. Steatosis and inflammatory infiltration resulting from chronic alcohol exposure occur through a TRPA1-independent mechanism.

What are the main findings?
Trpa1 mRNA is expressed in mouse hepatocytes and liver macrophages.Acetaldehyde is able to activate human TRPA1.Alcohol-induced liver inflammatory infiltration and steatosis are mediated through a TRPA1-independent mechanism in mice.

Trpa1 mRNA is expressed in mouse hepatocytes and liver macrophages.

Acetaldehyde is able to activate human TRPA1.

Alcohol-induced liver inflammatory infiltration and steatosis are mediated through a TRPA1-independent mechanism in mice.

What are the implications of the main findings?
The occurrence of Trpa1 in hepatocytes and liver macrophages suggested the role of this ion channel in inflammatory, fibrotic, and degenerative processes in the liver.The ability of acetaldehyde to activate human TRPA1 suggests that the ion channel might act as a mediator of alcohol-induced liver damage.Although steatosis and inflammatory infiltration resulting from chronic alcohol exposure are thought to occur through a TRPA1-independent mechanism, we hypothesize that the ion channel plays a role in alcohol-induced liver damage, particularly in late-stage fibrotic changes.

The occurrence of Trpa1 in hepatocytes and liver macrophages suggested the role of this ion channel in inflammatory, fibrotic, and degenerative processes in the liver.

The ability of acetaldehyde to activate human TRPA1 suggests that the ion channel might act as a mediator of alcohol-induced liver damage.

Although steatosis and inflammatory infiltration resulting from chronic alcohol exposure are thought to occur through a TRPA1-independent mechanism, we hypothesize that the ion channel plays a role in alcohol-induced liver damage, particularly in late-stage fibrotic changes.

Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel, and its activator, the alcohol breakdown product acetaldehyde, plays a key role in the pathomechanism of alcoholic liver disease (ALD). We hypothesized that TRPA1 is expressed in the liver, can be activated by alcohol breakdown products, and plays a role in ALD. We aimed (1) to confirm the presence of TRPA1 in liver samples from C57BL6/J mice by RNAscope in situ hybridization combined with immunostaining, (2) to prove that alcohol breakdown products may activate human TRPA1 by calcium-imaging, and (3) to investigate the role of TRPA1 in a chronic continuous 20% alcohol drinking model involving Trpa1 gene-deficient (KO) mice. The liver enzyme levels were evaluated; moreover, the steatosis, portal and interface inflammatory infiltrations were assessed in PAS–hematoxylin-stained sections. We detected Trpa1 expression in both hepatocytes and liver macrophages. We observed elevated liver enzyme levels in wild-type mice. Significant inflammatory infiltration and steatosis developed in both WT and KO mice in response to alcohol; however, no significant differences were found between the genotypes. We conclude that Trpa1 is expressed in hepatocytes and liver macrophages; however, the chronic alcohol-induced steatosis and inflammatory infiltration develop through a TRPA1-independent mechanism.