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Gene expression and DNA methylation changes in BeWo cells dependent on tumor necrosis factor-α and insulin-like growth factor-I
- Source :
- Human Cell. 33:37-46
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_treatment
Gene Expression
Biology
Transcriptome
03 medical and health sciences
Insulin-like growth factor
0302 clinical medicine
Gene expression
medicine
Humans
Epigenetics
Insulin-Like Growth Factor I
Tumor Necrosis Factor-alpha
Microarray analysis techniques
Trophoblast
Cell Biology
DNA Methylation
Molecular biology
NFKBIE
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
embryonic structures
DNA methylation
Subjects
Details
- ISSN :
- 17490774
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Human Cell
- Accession number :
- edsair.doi.dedup.....647e002e5f15d869cf900a0dd37869b1