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Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo

Authors
 Bu-Yeo Kim  ;  Minjeong Kim  ;  Ji Seong Jeong  ;  Sun-Ha Jee  ;  Il-Hyun Park  ;  Byung-Chul Lee  ;  Sun-Ku Chung  ;  Kyung-Min Lim  ;  Yun-Sil Lee 
Citation
 ENVIRONMENTAL RESEARCH, Vol.173 : 124-134, 2019 
Journal Title
 ENVIRONMENTAL RESEARCH 
ISSN
 0013-9351 
Issue Date
2019
MeSH
Animals ; Benzhydryl Compounds/toxicity* ; Hep G2 Cells ; Humans ; Liver ; Phenols/toxicity* ; Rats ; Transcriptome*
Keywords
Bisphenol A ; Hepatocyte spheroid ; Lipid metabolism ; Rat ; Transcriptomics
Abstract
Bisphenol A (BPA), a synthetic monomer commonly included in the daily products, has a structure similar to the estrogen receptor agonist. Therefore BPA has been anticipated to interfere with the hormone metabolisms and cause diverse pathological conditions. But the effects of BPA on the genetic landscapes of liver or hepatic cells have not been fully established. Gene expressional changes induced by low- or high-dose of BPA were evaluated in 3D cultured human hepatoma cells (HepG2 spheroids) in vitro at 0, 0.5, 5 and 200 μM and liver of rats exposed to BPA at 0, 0.5 and 250 mg/kg for 90 days in vivo. Functional enrichment analysis, pathway activity measurement and network analysis were performed using BPA-responsive genes. Treatment with BPA changed a lot of gene expressions in both HepG2 spheroids and rat livers depending on doses of BPA. Functional enrichment and pathway analysis show that lipid or steroid metabolism-related functions were altered by BPA in both HepG2 spheroids and livers of rats. Lipid metabolism-related functions altered by BPA formed a large cluster encompassing lipid biosynthesis, steroid metabolic process and cholesterol regulation process. It was also observed that distribution of pathway activities was correlated between HepG2 spheroids and rat livers at low-dose of BPA. Distance distribution in protein-protein interaction network also evidenced the closeness of BPA-responsive genes to metabolism pathways which include lipid metabolism. Collectively, we demonstrated that BPA greatly influenced overall gene expression and biological functions in both human hepatoma spheroids and rat liver, in which lipid- or steroid metabolism-associated genes were significantly altered by the exposure to BPA.
Full Text
https://www.sciencedirect.com/science/article/pii/S001393511930163X
DOI
10.1016/j.envres.2019.03.035
Appears in Collections:
4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원) > 1. Journal Papers
Yonsei Authors
Jee, Sun Ha(지선하) ORCID logo https://orcid.org/0000-0001-9519-3068
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/174750
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