Gene expression and DNA methylation changes in BeWo cells dependent on tumor necrosis factor-α and insulin-like growth factor-I

Pregnant women with increased insulin resistance, characterized by elevated levels of tumor necrosis factor-alpha (TNF-α) and insulin-like growth factor-I (IGF-I), are at high risk of preeclampsia. We hypothesized that TNF-α and IGF-I affect the placentas and cause pathological changes leading to pr...

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Bibliographic Details
Published in:Human cell : official journal of Human Cell Research Society 2020, Vol.33 (1), p.37-46
Main Authors: Tanaka, Kei, Nakabayashi, Kazuhiko, Kawai, Tomoko, Tanigaki, Shinji, Matsumoto, Kenji, Hata, Kenichiro, Kobayashi, Yoichi
Format: Article
Language:English
Subjects:
Arachidonic acid
Biomedical and Life Sciences
Cell Biology
CpG islands
Deoxyribonucleic acid
DNA
DNA methylation
DNA microarrays
Gene expression
Gynecology
Insulin
Insulin resistance
Insulin-like growth factor I
Insulin-like growth factors
Life Sciences
Major histocompatibility complex
NF-κB protein
Oncology
Placenta
Pre-eclampsia
Pregnancy
Reproductive Medicine
Research Article
Stem Cells
Surgery
Tumor necrosis factor-TNF
Tumor necrosis factor-α
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Summary:Pregnant women with increased insulin resistance, characterized by elevated levels of tumor necrosis factor-alpha (TNF-α) and insulin-like growth factor-I (IGF-I), are at high risk of preeclampsia. We hypothesized that TNF-α and IGF-I affect the placentas and cause pathological changes leading to preeclampsia. To understand the genetic and epigenetic effects of TNF-α and IGF-I on trophoblast cells, gene expression microarray and DNA methylation array of BeWo cells stimulated by TNF-α (100 pg/ml, 100 ng/ml) and IGF-I (100 ng/ml) were conducted. Microarray analysis revealed the differential gene expression patterns in BeWo cells co-stimulated by TNF-α and IGF-I. Enrichment analysis identified the terms associated with NF-kappa B signaling pathways and arachidonic acid cascades such as PTGS2 and PTGER2. DNA methylation array revealed the distinct CpG methylation pattern in BeWo cells stimulated by high-TNF-α and IGF-I, while neither of them showed independent effects. Enrichment analysis identified the terms associated with major histocompatibility complex proteins. Integration of transcriptome and DNA methylome analyses identified three differentially expressed genes with significant DNA methylation change: C3, GP1BA, and NFKBIE, which are all possibly associated with pathogenesis of preeclampsia. In conclusion, co-stimulation of TNF-α and IGF-I induced the genetic and epigenetic changes associated with preeclampsia in BeWo cells. The results suggested that BeWo cells stimulated by TNF-α and IGF-I is a good in vitro model of preeclamptic placenta in pregnancy with increased insulin resistance.
ISSN:1749-0774
0914-7470
1749-0774
DOI:10.1007/s13577-019-00299-5