Citation

Material Information

Title:
Transforming growth factor beta1 targets estrogen receptor signaling in bronchial epithelial cells
Creator:
L. Cody Smith
Santiago Moreno
Lauren Robertson
Sarah Robinson
Kristal Gant
Andrew J. Bryant
Tara Sabo-Attwood
Publisher:
BMC, Respiratory Research
Publication Date:
Language:
English

Subjects

Subjects / Keywords:
Transforming growth factor beta ( fast )
Estrogen ( fast )
Estrogen receptor ( fast )
Lung ( fast )
Fibrosis ( fast )

Notes

Abstract:
Background: Sex differences in idiopathic pulmonary fibrosis (IPF) suggest a protective role for estrogen (E2); however, mechanistic studies in animal models have produced mixed results. Reports using cell lines have investigated molecular interactions between transforming growth factor beta1 (TGF-β1) and estrogen receptor (ESR) pathways in breast, prostate, and skin cells, but no such interactions have been described in human lung cells. To address this gap in the literature, we investigated a role for E2 in modulating TGF-β1-induced signaling mechanisms and identified novel pathways impacted by estrogen in bronchial epithelial cells. Methods: We investigated a role for E2 in modulating TGF-β1-induced epithelial to mesenchymal transition (EMT) in bronchial epithelial cells (BEAS-2Bs) and characterized the effect of TGF-β1 on ESR mRNA and protein expression in BEAS-2Bs. We also quantified mRNA expression of ESRs in lung tissue from individuals with IPF and identified potential downstream targets of E2 signaling in BEAS-2Bs using RNA-Seq and gene set enrichment analysis. Results: E2 negligibly modulated TGF-β1-induced EMT; however, we report the novel observation that TGF-β1 repressed ESR expression, most notably estrogen receptor alpha (ESR1). Results of the RNA-Seq analysis showed that TGF-β1 and E2 inversely modulated the expression of several genes involved in processes such as extracellular matrix (ECM) turnover, airway smooth muscle cell contraction, and calcium flux regulation. We also report 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. Conclusions: Collectively, these results suggest that E2 influences unexplored pathways that may be relevant to pulmonary disease and highlights potential roles for E2 in the lung that may contribute to sex-specific differences. Keywords: Transforming growth factor beta1, Estrogen, Estrogen receptor, Lung, Fibrosis
General Note:
Smith et al. Respiratory Research (2018) 19:160 https://doi.org/10.1186/s12931-018-0861-5; Pages 1-17

Record Information

Source Institution:
University of Florida
Holding Location:
University of Florida
Rights Management:
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

UFDC Membership

Aggregations:
University of Florida Institutional Repository