# Mechanisms of Airway Epithelial Injury and Response

> **NIH NIH SC1** · NORTH CAROLINA AGRI & TECH ST UNIV · 2021 · $360,000

## Abstract

ABSTRACT
Cigarette smoking is the leading cause of chronic obstructive pulmonary disease (COPD); however, other
exposures, such as occupational exposure to indoor pollution accounts for 20-25% of COPD cases in the
United States. Exposure to organic dusts within swine confinement facilities (SCF) is a significant modifiable
risk factor for lung disease in SCF workers. Numerous reports recognize the association between repetitive
SCF organic dust exposure and development of a broad spectrum of chronic inflammatory lung diseases
including chronic bronchitis (CB) – one of two major forms of COPD. However, the cellular and molecular
mechanisms governing development of agriculture-related CB remain unclear. Challenges in the field of
agriculture-related lung disease research include the difficulty in recreating SCF exposure conditions and the
lack of physiologically relevant animal models to study `real world' exposures. Our preliminary data show that
SCF pigs are a model for early airway epithelium injury and response, as evidenced by phenotypic lesions
characteristic of CB including increased levels of the secreted airway mucins, airways contain goblet cell
hyperplasia, inflammation, and evidence of smooth muscle hypertrophy compared to non-SCF (pasture) pigs.
In this proposal, we will investigate mechanisms of airway epithelial injury and response to SCF organic dust
by comparing the behavior of lung tissue from SCF and non-SCF pigs. To identify sources of inflammatory
mediators, responses of lung leukocytes, lung slices and porcine tracheobronchial epithelial (PTBE) cells from
SCF and non-SCF to endotoxin will be compared (Aim 1). The calcium/calmodulin-dependent protein kinase II
(CaMKII), a kinase regulated by oxidative stress and implicated in pulmonary fibrosis, is more abundant in
airway epithelial tissue of SCF pigs compared to non-SCF pigs. Therefore, studies using various inhibitors will
be conducted to determine the role of CaMKII and oxidative stress in activation of airway inflammation
pathways, including nuclear factor kappa B, using PTBE cells from SCF pigs (Aim 2). Given the observance of
goblet cell hyperplasia in the airway epithelia of SCF pigs, we will utilize comprehensive proteomics
approaches to identify molecular pathways associated with goblet cell hyperplasia in porcine models (Aim 3).
Utilizing global and targeted proteomics approaches, pathways governing initiation and progression of goblet
cell hyperplasia and mucus secretion will be identified. Knowledge of molecular pathways that regulate goblet
cell hyperplasia will serve as potential targets for development of novel therapeutic strategies to treat CB
affecting agricultural workers and the general population.

## Key facts

- **NIH application ID:** 10240595
- **Project number:** 5SC1HL150742-03
- **Recipient organization:** NORTH CAROLINA AGRI & TECH ST UNIV
- **Principal Investigator:** Jenora Waterman
- **Activity code:** SC1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $360,000
- **Award type:** 5
- **Project period:** 2019-09-23 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240595

## Citation

> US National Institutes of Health, RePORTER application 10240595, Mechanisms of Airway Epithelial Injury and Response (5SC1HL150742-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10240595. Licensed CC0.

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