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Impacts of early life wildfire exposure on WNT pathway signaling molecules and the developing distal airways of rhesus macaques
- Sivaprasad, Meghna
- Advisor(s): Miller, Lisa
Abstract
With the advent of anthropogenically driven climate change, there is growing concern about the increasing severity of wildfires worldwide. Exposure to wildfire smoke has emerged as a critical public health issue, particularly for infants, whose developing lungs are highly vulnerable to pulmonary injury. While the overall effects of wildfire air pollutants on adult populations have been extensively studied, revealing significant impacts on respiratory and cardiovascular health, the implications of wildfire smoke on the particularly vulnerable infant population, and its consequences for lung development and function, remain largely unknown.Previous studies conducted by our research group using a rhesus macaque model have shown dysregulations in the expression of molecules involved in WNT pathway signal transduction in response to ozone exposure, a common secondary pollutant from wildfire smoke. This pathway plays a major role in lung development, suggesting that wildfire air pollutants such as PM2.5 may modulate WNT signaling in the lungs, potentially affecting distal airway development. In this study, we hypothesize that early-life wildfire smoke exposure is associated with altered alveolar growth and dysregulation of WNT pathway signaling molecules in the lungs of infant rhesus macaques. Lung tissue from a cohort of infants housed outdoors during the 2018 Camp Fire in Northern California (n=4, 5–6 months old) and indoor housed age-matched archived control animals (n=4, 6 months old), were used for this study. Biospecimens were analyzed for WNT11 and WNT3a expression using immunohistochemical techniques, western blots, and RT- qPCR, and overall alveolar growth was assessed using morphometric techniques. Our findings indicate that wildfire smoke exposure was associated with alterations in the expression of molecules in the WNT pathway at the protein, gene, and tissue levels, with increased expression of non-canonical WNT signaling molecules (WNT11) and decreased expression in canonical signaling molecules (WNT3a) compared to indoor housed controls. However, analysis of the distal airways showed no significant changes in morphometric parameters of alveolar growth, suggesting that the short-term exposure to wildfire smoke, as assessed within the parameters of this study, was not associated with alterations in distal lung development.
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