Rationale: Numerous epidemiological studies suggest adverse effects of air pollution exposure on lung function in pediatric populations. It is currently unknown how air pollutants, either singly or in combination, can alter lung function. Using a rhesus macaque monkey model, we have previously reported that early life ozone exposure results in a significant reduction of nonalveolarized airway generations, suggesting that alterations in distal airway development may contribute to lung function decrements. Transcriptomics data from rhesus monkey airway epithelium and mouse lung indicate a peak of expression for Wnt11 during early life, implicating a potential role for this non-canonical member in normal lung development. In this study, we hypothesized that early life ozone exposure may dysregulate Wnt11 expression in the infant lung.
Methods: We evaluated lung biospecimens obtained from rhesus monkeys after 5 months of experimental episodic ozone exposure at 0.5 parts per million(ppm), starting at either one month of age or thirty-one months of age. Animals were evaluated as infants (6 months of age) or young adults (36 months of age) (n = 6 per group). Lung tissue specimens were evaluated for Wnt11 expression using immunohistochemistry, western blot, and qRT-PCR.
Results: At 6 months of age, filtered air control and experimental animals demonstrated Wnt11 staining in fibroblasts and additional untested for cell types in distal airways. A difference in Wnt11 mRNA was detected in micro-dissected airways between the two groups, with ozone exposed animals having a 2-fold increase compared to filtered air control. Western blot analysis of whole lung homogenates from 6-month-old animals showed a higher density of Wnt11 protein in association with cyclic ozone exposure relative to filtered air controls.
Conclusions: We have found that early life ozone exposure results in a dysregulated expression of Wnt11 in the infant lung, with evidence of an overall increase in protein.
|Advisor:||Miller, Lisa A|
|Commitee:||Pinkerton, Kent E, Zeki, Amir A|
|School:||University of California, Davis|
|Department:||Pharmacology and Toxicology|
|School Location:||United States -- California|
|Source:||MAI 81/4(E), Masters Abstracts International|
|Keywords:||Lung, Ozone, Wnt11|
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