# Effects of arsenic and arsenic-containing mine tailings dust on airway epithelium and susceptibility to mold exposure

> **NIH ES P42** · UNIVERSITY OF ARIZONA · 2026 · $468,247

## Abstract

PROJECT SUMMARY (Project 1: Chen) 
Chronic exposure to arsenic (As), commonly found in mine tailings particulate matters (mt-PMs), heightens the 
risk of lung diseases. This risk is notably elevated for those living near contaminated sites due to continuous 
exposure from inhaling dust and consuming tainted water or food. Additionally, environmental stressors, such 
as mold, intensify these risks. At present, there is limited data about the mechanisms and effects of these 
exposures, especially regarding nonmalignant lung diseases. In previously published research, we found that 
As inhibited the production of major mucins, essential components for mucociliary clearance (MCC), in 
differentiated human airway epithelial cells (HAECs). Moreover, mouse models exposed to inhaled synthetic 
arsenic-containing dusts (sACDs) and real-life mt-PMs showed reduced CC16 expression, another crucial 
MCC component. A decrease in CC16, a significant biomarker, is correlated with impaired lung function in 
various diseases. Importantly, As appeared to repress retinoic acid (RA) signaling, leading to the 
downregulation of both mucins and CC16. In our preliminary studies for this proposal, we extended the 
previous findings by revealing that As-exposed HAECs underwent a process of de-differentiation. This change 
resulted in the repression of several secretory and ciliated cell markers, suggesting a pronounced MCC 
deficiency (MCCD) and a compromised epithelial barrier. Notably, all-trans retinoic acid (t-RA) could counteract As's effects, underscoring the significance of the RAR/RXR signaling pathway. Furthermore, Nrf2's 
involvement was essential for RAR/RXR degradation, and a deficiency in CC16 rendered mice more 
susceptible to mold exposure. Based on these insights, we hypothesize that As exposure induces MCCD in the 
airway epithelium through a crosstalk between Nrf2 and RAR/RXR. This dysfunction likely weakens the 
protective barrier, increasing susceptibility to environmenta

## Key facts

- **NIH application ID:** 11375919
- **Project number:** 5P42ES004940-37
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Yin  Chen
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** ES
- **Fiscal year:** 2026
- **Award amount:** $468,247
- **Award type:** 5
- **Project period:** 1997-04-01T00:00:00 → 2030-01-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11375919

## Citation

> US National Institutes of Health, RePORTER application 11375919, Effects of arsenic and arsenic-containing mine tailings dust on airway epithelium and susceptibility to mold exposure (5P42ES004940-37). Retrieved via AI Analytics 2026-07-10 from https://api.ai-analytics.org/grant/nih/11375919. Licensed CC0.

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