HSD17B14
17-beta-hydroxysteroid dehydrogenase 14 (EC 1.1.1.62) (17-beta-HSD 14) (17-beta-hydroxysteroid dehydrogenase DHRS10) (Dehydrogenase/reductase SDR family member 10) (Retinal short-chain dehydrogenase/reductase retSDR3) (Short chain dehydrogenase/reductase family 47C member 1) [DHRS10] [SDR3] [SDR47C1] [UNQ502/PRO474]
Publications[править]
Experimental and/or epidemiological studies suggest that prenatal exposure to bisphenol A (BPA) may delay fetal lung development and maturation and increase the susceptibility to childhood respiratory disease. However, the underlying mechanisms remain to be elucidated. In our previous study with cultured human fetal lung fibroblasts (HFLF), we demonstrated that 24-h exposure to 1 and 100 µM BPA increased GPR30 protein in the nuclear fraction. Exposure to 100 μM BPA had no effects on cell viability, but increased cytoplasmic expression of ERβ and release of GDF-15, as well as decreased release of IL-6, ET-1, and IP-10 through suppression of NFκB phosphorylation. By performing global gene expression and pathway analysis in this study, we identified molecular pathways, gene networks, and key molecules that were affected by 100, but not 0.01 and 1 µM BPA in HFLF. Using multiple genomic and proteomic tools, we confirmed these changes at both gene and protein levels. Our data suggest that 100 μM BPA increased CYP1B1 and HSD17B14 gene and protein expression and release of endogenous estradiol, which was associated with increased ROS production and DNA double-strand breaks, upregulation of genes and/or proteins in steroid synthesis and metabolism, and activation of Nrf2-regulated stress response pathways. In addition, BPA activated ATM-p53 signaling pathway, resulting in increased cell cycle arrest at G1 phase, senescence and autophagy, and decreased cell proliferation in HFLF. The results suggest that prenatal exposure to BPA at certain concentrations may affect fetal lung development and maturation, and thereby affecting susceptibility to childhood respiratory diseases.
MeSH Terms
- 17-Hydroxysteroid Dehydrogenases
- Air Pollutants, Occupational
- Autophagy
- Benzhydryl Compounds
- Cell Cycle Checkpoints
- Cellular Senescence
- Cytochrome P-450 CYP1B1
- Estradiol
- Fibroblasts
- Humans
- Lung
- NF-E2-Related Factor 2
- Phenols
- Reactive Oxygen Species
- Tumor Suppressor Protein p53
- Up-Regulation
Keywords
- ATM signaling
- Autophagy
- Bisphenol A
- CYP1B1
- Cell cycle arrest
- DNA double-strand breaks
- Estradiol release
- G1/S transition
- HSD17B14
- Human fetal lung fibroblasts
- Nrf2
- ROS
- Senescence
- Steroid synthesis and metabolism
- p53
- γ-H2AX