# Short-term exposure to a high-humidity environment triggers intestinal inflammation via AQP3

**Authors:** Jian Song, Xinhua Huang, Yi Luo, Mengjun Li, Yulin Ouyang, Wanli Liu, Hudan Pan, Huanhuan Luo

PMC · DOI: 10.3389/fimmu.2025.1563602 · 2025-06-18

## TL;DR

Short-term exposure to high humidity causes intestinal inflammation in mice, primarily through the action of the protein AQP3.

## Contribution

This study reveals a novel mechanism by which high humidity triggers intestinal inflammation via AQP3 activation.

## Key findings

- High humidity increased AQP3 and decreased AQP4 expression in the colon of wild-type mice.
- The TLR4/NF-κb/IL-6 inflammatory pathway was activated in mice exposed to high humidity.
- Aqp3 knockout mice showed reduced inflammation and oxidative stress markers in the colon.

## Abstract

With the increasing greenhouse effect, there is growing concern about the correlation between the humid environment and the incidence of various diseases. A high-humidity environment may cause intestinal inflammation through bacterial colonization or contamination of water. Aquaporin-3 (AQP3) plays an important role in maintaining intestinal water transport, permeability, fluid secretion, and absorption homeostasis. This paper explored the effects of short-term exposure to a high-humidity environment on intestinal health.

To explore the effects of a high-humidity environment on the intestine, we kept wild-type mice and Aqp3 knockout (Aqp3-/-
) mice in an artificial climatic box with 90(± 5) % humidity setting for a fortnight and recorded their body weights, food intake, water intake, and fur changes during the experiment. On the fourteenth day, colon tissues were collected to detect the expression of intestinal inflammatory factors, glutathione (GSH), malondialdehyde (MDA), water evaporator proteins (AQPs), and intestinal pathological changes by polymerase chain reaction (PCR), Western blotting analysis, and histopathological analysis.

The results showed that mice with short-term exposure to a high-humidity environment showed a significant increase in the expression of AQP3 and a significant decrease in the expression of AQP4 in the colon, and the TLR4/NF-κb/IL-6 pathway was activated. In Aqp3-/-
 mice, their colonic GSH expression was increased, MDA expression was decreased, and intestinal TLR4/NF-κb/IL-6 expressions were also decreased.

This study demonstrated the high-humidity environment induces an intestinal inflammatory response through AQP3, providing persuasive evidence for the pathogenesis of environmentally related diseases.

## Linked entities

- **Genes:** AQP3 (aquaporin 3 (Gill blood group)) [NCBI Gene 360], AQP4 (aquaporin 4) [NCBI Gene 361], TLR4 (toll like receptor 4) [NCBI Gene 7099], NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790], IL6 (interleukin 6) [NCBI Gene 3569]
- **Proteins:** AQP3 (aquaporin 3 (Gill blood group)), AQP4 (aquaporin 4), TLR4 (toll like receptor 4), NFKB1 (nuclear factor kappa B subunit 1), IL6 (interleukin 6), LOC23687505 (pyrimidodiazepine synthase), so (sine oculis)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Aqp4 (aquaporin 4) [NCBI Gene 11829] {aka WCH4}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Aqp3 (aquaporin 3) [NCBI Gene 11828] {aka AQP-2}
- **Diseases:** inflammation (MESH:D007249)
- **Chemicals:** GSH (MESH:D005978), MDA (MESH:D008315), water (MESH:D014867)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12258048/full.md

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Source: https://tomesphere.com/paper/PMC12258048