# ATP-related purinergic signaling via P2Y12 contributes to airway epithelial barrier integrity

**Authors:** Kota Tsuya, Shuichiro Maruoka, Shinichi Okamoto, Sotaro Shikano, Mari Ujike, Shiho Yamada, Yusuke Kurosawa, Kenji Mizumura, Yutaka Kozu, Yasuhiro Gon

PMC · DOI: 10.1186/s12860-026-00578-8 · BMC Molecular and Cell Biology · 2026-02-25

## TL;DR

ATP signaling through P2Y12 receptors helps maintain the integrity of airway epithelial barriers, which is important in conditions like asthma.

## Contribution

The novel contribution is identifying P2Y12 as a key receptor in ATP-related signaling that enhances airway epithelial barrier integrity.

## Key findings

- ATP improves airway epithelial barrier integrity in a dose-dependent manner.
- ATP increases expression of junction proteins like E-cadherin and occludin.
- P2Y12 is implicated in ATP-related signaling that supports barrier function.

## Abstract

The airway epithelial barrier, which defends against external pathogens, is compromised in bronchial asthma. This study investigated the roles of adenosine triphosphate (ATP) and specific purinergic receptors in airway epithelial barrier function. Using the 16HBE14o- human airway epithelial cell line, we measured barrier integrity using transepithelial electrical resistance and the apparent paracellular permeability coefficient.

ATP enhanced barrier integrity in a dose-dependent manner without affecting cell proliferation. Real-time PCR revealed an increased expression of tight and adherens junction proteins, including E-cadherin and occludin, following ATP stimulation. Our findings suggest that P2Y12 contributes to ATP-related purinergic signaling associated with enhanced airway epithelial barrier integrity.

These findings suggest that ATP-related purinergic signaling via P2Y12 may contribute to the regulation of airway epithelial barrier integrity in vitro. Further studies in more physiologically relevant systems are warranted to determine the clinical relevance of these observations.

## Linked entities

- **Genes:** shg (shotgun) [NCBI Gene 37386], si:ch73-61d6.3 (uncharacterized si:ch73-61d6.3) [NCBI Gene 103182021]
- **Proteins:** P2RY12 (purinergic receptor P2Y12)
- **Chemicals:** adenosine triphosphate (PubChem CID 5957), ATP (PubChem CID 5957)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** P2RY12 (purinergic receptor P2Y12) [NCBI Gene 64805] {aka ADPG-R, BDPLT8, HORK3, P2T(AC), P2Y(12)R, P2Y(AC)}
- **Chemicals:** ATP (MESH:D000255)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13041268/full.md

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Source: https://tomesphere.com/paper/PMC13041268