Global transcriptomic analyses of bronchial epithelial cells exposed to 5 ng/mL TGF-β1 and 10 nM Estrogen individually and in combination. Homo sapiens

To begin to identify downstream consequences of TGF-β1-induced reduction of estrogen receptor expression, we employed RNA-Seq. Results of global transcriptomic analysis showed that TGF-β1 and E2 inversely modulated the expression of several genes involved in both known pro-fibrotic cellular processes such as extracellular matrix turnover and newly identified events including airway smooth muscle cell contraction and calcium flux regulation. We also report, for the first time, that E2 specifically modulated the expression of genes involved in chromatin remodeling pathways and that this regulation was absent in the presence of TGF-β1. Collectively, these results suggest that E2 influences pathways relevant to pulmonary fibrosis and highlights potential roles for E2 in the lung that may contribute to sex-specific differences in IPF. Overall design: Four treatment groups were analyzed; cells exposed to vehicle control (n = 5), 5 ng/mL TGF-β1 (n = 5), 10 nM Estrogen (n = 3), or 5 ng/mL TGF-β1 and 10 nM Estrogen in combination (n = 4)