Modeling Human Lung Cells Exposure to Wildfire Uncovers Aberrant lncRNAs Signature

Emissions generated by wildfires are a growing threat to human health and are characterized by a unique chemical composition that is tightly dependent on geographic factors such as fuel type. Long noncoding RNAs (lncRNAs) are a class of RNA molecules proven to be critical to many biological processes, and their condition-specific expression patterns are emerging as prominent prognostic and diagnostic biomarkers for human disease. We utilized a new air-liquid interface (ALI) direct exposure system that we designed and validated in house to expose immortalized human tracheobronchial epithelial cells (AALE) to two unique wildfire smokes representative of geographic regions (Sierra Forest and Great Basin). We conducted an RNAseq analysis on the exposed cell cultures and proved through both principal component and differential expression analysis that each smoke has a unique effect on the LncRNA expression profiles of the exposed cells when compared to the control samples. Our study proves that there is a link between the geographic origin of wildfire smoke and the resulting LncRNA expression profile in exposed lung cells and also serves as a proof of concept for the in-house designed ALI exposure system. Our study serves as an introduction to the scientific community of how unique expression patterns of LncRNAs in patients with wildfire smoke-related disease can be utilized as prognostic and diagnostic tools, as the current roles of LncRNA expression profiles in wildfire smoke-related disease, other than this study, are completely uncharted

MicroRNA-22 Is a Key Regulator of Lipid and Metabolic Homeostasis

Obesity is a growing public health problem associated with increased risk of type 2 diabetes, cardiovascular disease, nonalcoholic fatty liver disease (NAFLD) and cancer. Here, we identify microRNA-22 (miR-22) as an essential rheostat involved in the control of lipid and energy homeostasis as well as the onset and maintenance of obesity. We demonstrate through knockout and transgenic mouse models that miR-22 loss-of-function protects against obesity and hepatic steatosis, while its overexpression promotes both phenotypes even when mice are fed a regular chow diet. Mechanistically, we show that miR-22 controls multiple pathways related to lipid biogenesis and differentiation. Importantly, genetic ablation of miR-22 favors metabolic rewiring towards higher energy expenditure and browning of white adipose tissue, suggesting that modulation of miR-22 could represent a viable therapeutic strategy for treatment of obesity and other metabolic disorders