Location: Arkansas Children's Nutrition CenterTitle: Early growth response protein 1 (EGR1) regulates pro-inflammatory gene expression in response to palmitate and TNF alpha in human placenta cells and is induced in obese placenta Author
Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 2/13/2013
Publication Date: 4/15/2013
Citation: Saben, J., Andres, A., Borengasser, S., Zhong, Y., Shankar, K. 2013. Early growth response protein 1 (EGR1) regulates pro-inflammatory gene expression in response to palmitate and TNF alpha in human placenta cells and is induced in obese placenta [abstract]. FASEB Journal. 27(Meeting Abstracts):109.8. Interpretive Summary:
Technical Abstract: Maternal obesity has been hypothesized to induce a pro-inflammatory response in the placenta. However, the specific factors contributing to this pro-infalmmatory response are yet to be determined. Our objective was to examine the effects of palmitic acid (PA), tumor necrosis factor alpha (TNF alpha), or a combination of both (PA + TNF alpha) on placental trophoblasts (Bewo cells). Microarray analysis revealed distinct gene expression signatures with increased expression of genes regulated by mitogen activated protein kinases (MAPK), or involved in inflammation, and in the immediate-early response after exposure to PA, TNF alpha, or PA + TNF alpha. An immediate-early response gene, early growth response I (EGRI), showed the largest increase in mRNA following treatment with PA and PA + TNF alpha ,and was regulated by transcription factors downstream of MAPKs. Knockdown of EGRI in placenta cells impaired the pro-inflammatory response to PA and PA + TNF alpha. Analysis of term placenta analysis also revealed elevated genes involved with inflammation in obese verses lean placenta. Our results indicate that increased circulating fatty acids and inflammatory cytokines associated with obesity may contribute to inflammation in placenta cells for which EGRI may be a key regulator.