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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

Title
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
Kim, Bu-YeoKim, MinjeongJeong, Ji SeongJee, Sun-HaPark, Il-HyunLee, Byung-ChulChung, Sun-KuLim, Kyung-MinLee, Yun-Sil
Ewha Authors
이윤실임경민김민정
SCOPUS Author ID
이윤실scopus; 임경민scopus; 김민정scopus
Issue Date
2019
Journal Title
ENVIRONMENTAL RESEARCH
ISSN
0013-9351JCR Link

1096-0953JCR Link
Citation
ENVIRONMENTAL RESEARCH vol. 173, pp. 124 - 134
Keywords
Bisphenol ATranscriptomicsLipid metabolismHepatocyte spheroidRat
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
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 mu M 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.
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DOI
10.1016/j.envres.2019.03.035
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약학대학 > 약학과 > Journal papers
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